diff --git a/CHANGELOG.md b/CHANGELOG.md
index a16778ad94..6fae288f74 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -39,6 +39,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 - [#613](https://github.com/nf-core/sarek/pull/613) - Added params `--vep_version` to allow more configuration on the vep container definition
 - [#620](https://github.com/nf-core/sarek/pull/620) - Added checks for sex information when running a CNV tools
 - [#623](https://github.com/nf-core/sarek/pull/623) - Additional checks of data in the input sample sheet.
+- [#629](https://github.com/nf-core/sarek/pull/629) - Added checks to catch inconsistency between supplied samples and requested tools.
 
 ### Changed
 
diff --git a/workflows/sarek.nf b/workflows/sarek.nf
index d46fbe5ea9..1b38654e69 100644
--- a/workflows/sarek.nf
+++ b/workflows/sarek.nf
@@ -1028,15 +1028,20 @@ def extract_csv(csv_file) {
             }
             if (!sample2patient.containsKey(row.sample.toString())) {
                 sample2patient[row.sample.toString()] = row.patient.toString()
-            } else if (sample2patient[row.sample.toString()] !== row.patient.toString()) {
+            } else if (sample2patient[row.sample.toString()] != row.patient.toString()) {
                 log.error('The sample "' + row.sample.toString() + '" is registered for both patient "' + row.patient.toString() + '" and "' + sample2patient[row.sample.toString()] + '" in the sample sheet.')
                 System.exit(1)
             }
         }
 
+    sample_count_all = 0
+    sample_count_normal = 0
+    sample_count_tumor = 0
+
     Channel.from(csv_file).splitCsv(header: true)
         //Retrieves number of lanes by grouping together by patient and sample and counting how many entries there are for this combination
         .map{ row ->
+            sample_count_all++
             if (!(row.patient && row.sample)){
                 log.error "Missing field in csv file header. The csv file must have fields named 'patient' and 'sample'."
                 System.exit(1)
@@ -1048,6 +1053,7 @@ def extract_csv(csv_file) {
             [rows, size]
         }.transpose()
         .map{ row, numLanes -> //from here do the usual thing for csv parsing
+
         def meta = [:]
 
         // Meta data to identify samplesheet
@@ -1066,6 +1072,34 @@ def extract_csv(csv_file) {
         if (row.status) meta.status = row.status.toInteger()
         else meta.status = 0
 
+        if (meta.status == 0) sample_count_normal++
+        else sample_count_tumor++
+
+        // Two checks for ensuring that the pipeline stops with a meaningful error message if
+        // 1. the sample-sheet only contains normal-samples, but some of the requested tools require tumor-samples, and
+        // 2. the sample-sheet only contains tumor-samples, but some of the requested tools require normal-samples.
+        if ((sample_count_normal == sample_count_all) && params.tools) { // In this case, the sample-sheet contains no tumor-samples
+            def tools_tumor = ['ascat', 'controlfreec', 'mutect2', 'msisensorpro']
+            def tools_tumor_asked = []
+            tools_tumor.each{ tool ->
+                if (params.tools.contains(tool)) tools_tumor_asked.add(tool)
+            }
+            if (!tools_tumor_asked.isEmpty()) {
+                log.error('The sample-sheet only contains normal-samples, but the following tools, which were requested with "--tools", expect at least one tumor-sample : ' + tools_tumor_asked.join(", "))
+                System.exit(1)
+            }
+        } else if ((sample_count_tumor == sample_count_all) && params.tools) {  // In this case, the sample-sheet contains no normal/germline-samples
+            def tools_requiring_normal_samples = ['ascat', 'deepvariant', 'haplotypecaller']
+            def requested_tools_requiring_normal_samples = []
+            tools_requiring_normal_samples.each{ tool_requiring_normal_samples ->
+                if (params.tools.contains(tool_requiring_normal_samples)) requested_tools_requiring_normal_samples.add(tool_requiring_normal_samples)
+            }
+            if (!requested_tools_requiring_normal_samples.isEmpty()) {
+                log.error('The sample-sheet only contains tumor-samples, but the following tools, which were requested by the option "tools", expect at least one normal-sample : ' + requested_tools_requiring_normal_samples.join(", "))
+                System.exit(1)
+            }
+        }
+
         // mapping with fastq
         if (row.lane && row.fastq_2) {
             meta.id         = "${row.sample}-${row.lane}".toString()