diff --git a/CHANGELOG.md b/CHANGELOG.md
index 074807bd..0a0f4119 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -14,6 +14,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 - MT del script to detect mitochondrial deletions [#349](https://github.com/nf-core/raredisease/pull/349)
 - eKLIPse to identify large mitochondrial deletions [#365](https://github.com/nf-core/raredisease/pull/365)
 - UPD+Chromograph to identify and visualize UPD sites and regions in the chromosomes [#364](https://github.com/nf-core/raredisease/pull/364) and [#366](https://github.com/nf-core/raredisease/pull/366)
+- Added check for presence of case id for each sample in samplesheet [#357](https://github.com/nf-core/raredisease/pull/357)
 
 ### Fixed
 
diff --git a/bin/check_samplesheet.py b/bin/check_samplesheet.py
index ac46acd3..90486cb6 100755
--- a/bin/check_samplesheet.py
+++ b/bin/check_samplesheet.py
@@ -38,6 +38,7 @@ def __init__(
         first_col="fastq_1",
         second_col="fastq_2",
         single_col="single_end",
+        case_id_col="case_id",
         **kwargs,
     ):
         """
@@ -53,6 +54,8 @@ def __init__(
             single_col (str): The name of the new column that will be inserted and
                 records whether the sample contains single- or paired-end sequencing
                 reads (default "single_end").
+            case_id_col (str): The name of the column that contains the case_id
+                (default "case_id").
 
         """
         super().__init__(**kwargs)
@@ -60,6 +63,7 @@ def __init__(
         self._first_col = first_col
         self._second_col = second_col
         self._single_col = single_col
+        self._case_id_col = case_id_col
         self._seen = set()
         self.modified = []
 
@@ -76,6 +80,7 @@ def validate_and_transform(self, row):
         self._validate_first(row)
         self._validate_second(row)
         self._validate_pair(row)
+        self._validate_case_id(row)
         self._seen.add((row[self._sample_col], row[self._first_col]))
         self.modified.append(row)
 
@@ -108,6 +113,13 @@ def _validate_pair(self, row):
         else:
             row[self._single_col] = True
 
+    def _validate_case_id(self, row):
+        """Assert that the case id exists and convert spaces to underscores."""
+        if len(row[self._case_id_col]) <= 0:
+            raise AssertionError("Case ID input is required.")
+        # Sanitize id slightly.
+        row[self._case_id_col] = row[self._case_id_col].replace(" ", "_")
+
     def _validate_fastq_format(self, filename):
         """Assert that a given filename has one of the expected FASTQ extensions."""
         if not any(filename.endswith(extension) for extension in self.VALID_FORMATS):