Trop2, a transmembrane protein reported to be overexpressed in various epithelial tumors and whose function has been elusive, is found to possess an unexpected tumor suppressor role. Trop2 knockout mice develop skin cancers upon exposure to carcinogens in collaboration with loss of the tumor suppressor gene, Arf. Tumors arising in this context are biphasic sarcomatoid carcinomas that possess both E-cadherin-positive squamous and vimentin-positive spindle cell histology. The photomicrograph shows immunofluorescence of a representative tumor possessing both E-cadherin positive (red) and E-cadherin-negative, vimentin-positive (green) cells corresponding to squamous and spindle cell histology respectively (not shown); nuclei are stained blue with 4′,6-diamidino-2-phenylindole. For further details, please see Wang and coworkers on page 1686 in this issue.