Using an approach based on the co-amplification of wild-type and exon deleted progesterone receptor (PR) variant cDNAs, we identified exon-deleted PR variant mRNAs in both normal and neoplastic human breast tissues. Several naturally occurring variants, whose sequences revealed precise whole exon deletions, may encode putative PR-like proteins which lack some functional domains of the wild-type PR molecule. We suggest that these PR variant proteins could have a pathophysiological role in progestin action, as suggested for estrogen receptor variant proteins.