Connor YD, Miao D, Lin DI, et al. - Given small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) and SMARCA4-deficient undifferentiated uterine sarcoma (SMARCA4-DUS) represent rare and aggressive tumors, mainly hitting pre- and perimenopausal women, and in most of these tumors, inactivating SMARCA4 mutations are considered to be the driving molecular events, so, researchers describe the clinical course of a family with germline SMARCA4 mutation and contrasted large cohorts of these rare tumor types. In a single family with an inherited germline SMARCA4 mutation, either SCCOHT or SMARCA4-DUS development happened in two different family members, and despite receiving aggressive surgical, chemotherapy and immunotherapy treatment, both members died within one year of diagnosis. Younger age and a greater likelihood of having germline SMARCA4 alterations were observed in SCCOHT patients vs SMARCA4-DUS patients, as shown in a retrospective comparative study of large SCCOHT (n = 48) and SMARCA4-DUS (n = 17) cohorts. Advised genetic testing and counseling in families with these tumor types may be informed by increasing knowledge on the role of SMARCA4 in the pathogenesis of these rare cancers.