Transin RNA is a 1.9-kilobase RNA transcript induced by oncogenes in rat embryo fibroblast cell lines. We show that RNA species complementary to a cloned transin cDNA are present in mouse skin squamous cell carcinomas induced by a classical initiation-promotion protocol but not in premalignant, benign papillomas or in normal epidermis. A single application of a tumor promoting phorbol ester to normal epidermis elicits a transient increase in these RNA levels. Transin RNA encodes a secreted protease, an activity consistent with a functional role for enhanced expression of transin RNA in the progression of benign, encapsulated tumors to malignant, invasive carcinomas.