Deposits of birefringent calcium oxalate crystals in the breast constitute a mammographically detectable but often histologically overlooked form of calcification. Unstained by routine dyes, these deposits are important as a cause of discrepant radiographic and microscopic biopsy findings. To elucidate the pathologic changes that give rise to these crystals and the possible significance of these deposits in the breast, we retrospectively studied 119 breast biopsies from 100 women. By polarized light microscopy, we identified 16 cases with calcium oxalate deposits from this group. The crystals were typically within benign cysts or terminal ductules exhibiting apocrine differentiation by conventional morphologic criteria or by immunoreactivity to monoclonal antibodies against gross cystic disease fluid protein of 1,500 MW (anti-GCDFP-15). The lesions harboring the crystals were papillary or cystic apocrine metaplasia in 14 cases and simple apocrine metaplasia in two cases. These lesions were associated with separate foci of lobular carcinoma in situ in three cases and with other proliferative lesions regarded as risk markers for invasive carcinoma in six other cases. Paradoxically, the crystals were rarely seen in association with infiltrating carcinomas. Our findings support the concept that calcium oxalate deposits are a secretory form of calcification. The association with lobular carcinoma in situ and the rarity of the crystals in invasive carcinomas are in accord with previous observations. We found polarized light microscopy indispensable for the demonstration of these deposits in hematoxylin-eosin-stained sections.