We identified mutations in cyclin D1 at Proline 287 in a diverse tumor set including melanoma, endometrial carcinoma, colonic adenocarcinoma, ovarian endometrioid adenocarcinoma, uterine leyomyosarcoma and squamous cell carcinoma of lung, oro-pharynx and skin, thus supporting the notion that CCND1 driver mutations at Pro287 may be a recurrent hotspot in cancer. Here, CCND1 is linked to squamous cell carcinoma.