In a study on gene deregulation in ovarian carcinoma we found a mRNA coding for a 350 kDa protein, Drop1, to be downregulated 20‐ to 180‐fold in the majority of ovarian and mammary carcinomas. The mRNA is encoded by a set of exons in the 5′ region of the SYNE1 gene. Immunohistochemical staining for Drop1 protein by a specific monoclonal antibody corresponds to the pattern seen for the mRNA. cDNA arrays of matched pairs of tumor and normal tissue and in situ hybridizations confirmed the drastic loss of Drop1 mRNA as a common feature in uterus, cervix, kidney, lung, thyroid and pancreas carcinomas, already at early tumor stages and in all metastases. Two‐hybrid studies suggest a role of this deficiency in the malignant progression of epithelial tumors. © 2008 Wiley‐Liss, Inc.