We describe 5 patients (mean age, 50 years; all had uterine bleeding) whose routine endometrial biopsy and curettage specimens contained prominent signet-ring cells. Each specimen contained loose aggregates of signet-ring cells scattered within the endometrial stroma that were characterized by peripherally displaced, small, uniform nuclei with indistinct nucleoli and showed no mitotic activity. The central portion of the cytoplasm was occupied by single or multiple cytoplasmic vacuoles. In all cases, the signet-ring cells were reactive for vimentin and negative for epithelial membrane antigen and cytokeratin. Four cases were focally positive for muscle-specific actin or smooth muscle actin and negative for CD68, Mac387, periodic acid-Schiff, mucicarmine, and alcian blue. In these 4 cases, the surrounding endometrial stroma showed decidual changes, and the signet-ring cells demonstrated a morphologic continuum with more typical decidualized stroma. As such, the signet-ring cells in these cases were vacuolated, decidualized endometrial stromal cells. In the remaining case, the vacuolar contents of the signet-ring cells were periodic acid-Schiff-positive and resistant to diastase predigestion, and the cells reacted with Mac387 and CD68. The surrounding stroma showed no decidual reaction. Thus, the signet-ring cells in this case were of histiocytic differentiation. Endometrial stroma occasionally may contain nonneoplastic signet-ring cells that closely mimic adenocarcinoma. At least 2 directions of differentiation, decidual and histiocytic, are possible.