Retinoids, vitamin A (retinol) and related metabolites, have been shown to be important in regulating cell growth and differentiation. We have shown that expression of the enzyme lecithin:retinol acyltransferase (LRAT), which converts retinol to retinyl esters, is reduced in several human carcinomas as compared with adjacent normal tissue from the same organs. The purpose of this research was to determine if aspects of retinoid signaling are impaired in human breast cancer. We evaluated LRAT protein expression in neoplastic and adjacent, non-neoplastic glandular breast tissue specimens from human patients. We evaluated 26 specimens from patients diagnosed with breast cancer between 2003 and 2005. Representative paraffin-embedded tissue blocks from each tumor, with each containing adjacent non-neoplastic glandular breast tissue, were examined by immunohistochemistry with affinity purified antibodies to human LRAT protein. LRAT protein was prominently detected throughout the non-neoplastic glandular breast tissue in all of the specimens. Areas of ductal carcinoma in situ and well-differentiated invasive breast carcinomas showed an intensity of staining with the LRAT antibody which was similar to that of the adjacent normal tissue. Expression of LRAT protein progressively decreased with a reduction in the degree of tumor differentiation in invasive breast carcinomas. LRAT protein levels correlate better with the degree of ductal tumor differentiation than does estrogen receptor status in this study. Furthermore, normal human breast epithelium exhibits intense LRAT staining, indicating a major role for LRAT in human breast physiology.