diff --git a/pkgs/development/python-modules/cnvkit/default.nix b/pkgs/development/python-modules/cnvkit/default.nix
index 4911f8b004cd..eb6375367297 100644
--- a/pkgs/development/python-modules/cnvkit/default.nix
+++ b/pkgs/development/python-modules/cnvkit/default.nix
@@ -3,9 +3,9 @@
   buildPythonPackage,
   fetchFromGitHub,
   fetchpatch,
-
+  python,
+  makeWrapper,
   # dependencies
-  R,
   biopython,
   matplotlib,
   numpy,
@@ -13,15 +13,15 @@
   pomegranate,
   pyfaidx,
   pysam,
-  rPackages,
   reportlab,
+  rPackages,
   scikit-learn,
   scipy,
-
+  R,
   # tests
   pytestCheckHook,
-}:
 
+}:
 buildPythonPackage rec {
   pname = "cnvkit";
   version = "0.9.12";
@@ -47,11 +47,38 @@ buildPythonPackage rec {
     "pomegranate"
   ];
 
-  # Numpy 2 compatibility
-  postPatch = ''
-    substituteInPlace skgenome/intersect.py \
-      --replace-fail "np.string_" "np.bytes_"
-  '';
+  nativeBuildInputs = [
+    makeWrapper
+  ];
+
+  buildInputs = [
+    R
+  ];
+
+  postPatch =
+    let
+      rscript = lib.getExe' R "Rscript";
+    in
+    # Numpy 2 compatibility
+    ''
+      substituteInPlace skgenome/intersect.py \
+        --replace-fail "np.string_" "np.bytes_"
+    ''
+    # Patch shebang lines in R scripts
+    + ''
+      substituteInPlace cnvlib/segmentation/flasso.py \
+        --replace-fail "#!/usr/bin/env Rscript" "#!${rscript}"
+
+      substituteInPlace cnvlib/segmentation/cbs.py \
+        --replace-fail "#!/usr/bin/env Rscript" "#!${rscript}"
+
+      substituteInPlace cnvlib/segmentation/__init__.py \
+        --replace-fail 'rscript_path="Rscript"' 'rscript_path="${rscript}"'
+
+      substituteInPlace cnvlib/commands.py \
+        --replace-fail 'default="Rscript"' 'default="${rscript}"'
+
+    '';
 
   dependencies = [
     biopython
@@ -61,12 +88,42 @@ buildPythonPackage rec {
     pomegranate
     pyfaidx
     pysam
-    rPackages.DNAcopy
     reportlab
+    rPackages.DNAcopy
     scikit-learn
     scipy
   ];
 
+  # Make sure R can find the DNAcopy package
+  postInstall = ''
+    wrapProgram $out/bin/cnvkit.py \
+      --set R_LIBS_SITE "${rPackages.DNAcopy}/library" \
+       --set MPLCONFIGDIR "/tmp/matplotlib-config"
+  '';
+
+  installCheckPhase = ''
+    runHook preInstallCheck
+
+    ${python.executable} -m pytest --deselect=test/test_commands.py::CommandTests::test_batch \
+      --deselect=test/test_commands.py::CommandTests::test_segment_hmm
+
+      cd test
+      # Set matplotlib config directory for the tests
+      export MPLCONFIGDIR="/tmp/matplotlib-config"
+      export HOME="/tmp"
+      mkdir -p "$MPLCONFIGDIR"
+
+      # Use the installed binary - it's already wrapped with R_LIBS_SITE
+      make cnvkit="$out/bin/cnvkit.py" || {
+        echo "Make tests failed"
+        exit 1
+      }
+
+    runHook postInstallCheck
+  '';
+
+  doInstallCheck = true;
+
   pythonImportsCheck = [ "cnvlib" ];
 
   nativeCheckInputs = [
@@ -74,13 +131,6 @@ buildPythonPackage rec {
     R
   ];
 
-  disabledTests = [
-    # AttributeError: module 'pomegranate' has no attribute 'NormalDistribution'
-    # https://github.com/etal/cnvkit/issues/815
-    "test_batch"
-    "test_segment_hmm"
-  ];
-
   meta = {
     homepage = "https://cnvkit.readthedocs.io";
     description = "Python library and command-line software toolkit to infer and visualize copy number from high-throughput DNA sequencing data";