We found that according to the CERES score, the transcription factor SOX9 is essential in melanoma cell lines, despite the fact these cell lines lack expression of SOX9 but highly express SOX10. We showed this was apparently caused by guides with a single-mismatch alignment to SOX10, causing off-target effects that confound the growth phenotype for SOX9 non-expressing cell lines. The gene discussed is SOX10; the disease is melanoma.