We have identified a messenger RNA coding for a variant estrogen receptor jointly expressed with the normal mRNA in the estrogen receptor-positive, -responsive mammary carcinoma cell lines MCF-7 and ZR 75-1 by means of reverse transcription polymerase chain reaction. This variant mRNA was not observed in estrogen receptor-negative, -unresponsive MDA-MB 231 cells. Partial sequence analysis of the variant complementary DNA revealed identity to sequences of the estrogen receptor exons 3, 5, and 6, but the absence of the entire exon 4. We suggest that this variant receptor messenger is created by alternative splicing. The variant protein is expected to lack most of the hinge domain and part of the hormone binding domain, and it might have a cellular distribution and estrogen-binding affinity different from that of the normal receptor protein.