Salivary duct carcinoma (SDC) is a high-grade neoplasm with marked morphological resemblance to mammary duct carcinoma. The novel estrogen receptor (ER)-interacting protein and the proline-, glutamic acid-, and leucine-rich protein 1 ( PELP1 ), also called the modulator of nongenomic activity of ER ( MNAR ), have been shown to activate steroid hormone receptors in mammary carcinomas by nongenomic and genomic mechanisms. The expression and the relationship of this gene to the ER status in SDCs are unknown. We investigated the differential expression of the PELP1 / MNAR and the ERs alpha and beta proteins in SDCs, using Western blotting and immunohistochemistry. Western blot analysis of 7 paired normal and tumor specimens showed increased expression of PELP1 / MNAR and ER beta in 3 and 4 of the SDCs, respectively. No detectable expression of ER alpha in any normal or SDC specimens was noted. Immunohistochemical staining performed on 70 SDCs revealed strong expression of PELP1 / MNAR in 51 (73%) and ER beta in 52 (74%) tumors. PELP1 / MNAR and ER beta were coexpressed in 35 (50%), individually in 17 (24.2%), and negative in 18 (25.7%) tumors. PELP1 / MNAR staining was predominantly cytoplasmic whereas ER beta staining was nuclear and occasionally cytoplasmic in tumor cells. Our results indicate that PELP1 / MNAR and ER beta are coexpressed in most SDCs and may play a role in the pathobiology of these tumors.