The proopiomelanocortin (POMC) gene is expressed in many normal nonpituitary tissues, in addition to the pituitary. POMC-derived peptides have also been detected in many pheochromocytomas. We examined poly(A)+ RNA from 5 pheochromocytomas with a POMC exon 3 riboprobe and show that 3 tumors contained POMC-like mRNAs that were 50 to 350 bases longer than pituitary POMC mRNA. S1 nuclease analyses of tumor poly(A)+ RNA demonstrate that some of the POMC-like mRNAs contain additional segments of 238, 318 or 374 nucleotides derived from the region immediately upstream from the normal transcription initiation site. We conclude that pheochromocytomas express the POMC gene and that the long POMC-like mRNAs in these tumors and, probably, those in normal adrenal and testis arise from transcription initiating at sites upstream from the normal site used in pituitary.