MMR‐deficient sebaceous lesions from MSH2 gene mutation carriers demonstrated a significantly higher tumor mutation burden, increased numbers of indels in exonic microsatellite repeats and the highest proportion of tumor mutational signatures 6 and 15 compared with MMR‐proficient non‐Lynch sebaceous lesions, features which are consistent with other cancer types demonstrating MMR‐deficiency. Here, MSH2 is linked to neoplasm.