Recurrent mutations in the CTNNB1 or APC genes leading to the activation of the Wnt/betacatenin pathway are observed in adnexal tumors with matrical differentiation. While most pilomatricomas arise sporadically and harbor CTNNB1 mutations, cutaneous hybrid cysts combining epidermal and matrical differentiations have been mostly reported in a context of the familial adenomatosis polyposis/Gardner's syndrome related to germinal mutations of APC. The objective of this study is to understand the pathogenesis of hybrid cysts combining epidermal and matrical differentiations. The 287 cases diagnosed as pilomatricoma/hybrid cysts registered between January 1, 2015 and February 21, 2023 in the Pathology Department at Tours University Hospital Center were considered for inclusion. After diagnosis confirmation, all cases were classified as pilomatricomas or hybrid cysts. Clinical data and microscopic features of the two groups were compared. Immunohistochemical detection of the betacatenin and CTNNB1/APC genes sequencing were performed in all hybrid cysts. Among the cohort, ten cases were classified as hybrid cysts (4%). None had a personal or familial history of familial adenomatosis polyposis. The immunochemistry confirmed a betacatenin nuclear expression in the matrical component in all excepted one cases, while no nuclear accumulation was observed in the epidermal component of most hybrid cysts (n = 8, 80%). CTNNB1 mutations were detected in all hybrid cysts with interpretable sequencing data (n = 7/10). By contrast, only a variant of uncertain significance (class 3) was detected in APC in association with a pathogenic CTNNB1 mutation in one case. Hybrid cysts are rare entities consisting in 4% of the tumors analyzed in our study. Our results suggest that most hybrid cysts occur sporadically and are associated with CTNNB1 somatic mutations.