Prostatic intraluminal crystalloids are irregular eosinophilic, non-birefringent structures increasingly recognized as potential indicators of prostatic malignancy. In a study of 250 randomly selected surgical pathology cases of prostatic tissues none of 50 cases of benign glandular hyperplasia (0%), one of 50 cases of atypical adenomatous hyperplasia, 18 of 50 cases of well-differentiated adenocarcinoma (36%), seven of 50 cases of moderately differentiated adenocarcinoma (14%), and none of 50 cases of poorly differentiated adenocarcinoma (0%) revealed intraluminal crystalloids. A histochemical and immunohistochemical staining panel indicated that the crystalloids were nonproteinaceous. Crystalloids were stained intensely with phosphotungstic acid hematoxylin and did not stain for prostatic-specific antigen or hemoglobin. Crystalloids were clearly differentiated from prostatic corpora amylacea on light microscopy, histochemistry, scanning, and transmission electron microscopy. Electron probe x-ray microanalysis of 10 cases of crystalloids revealed uniform high sulfur peaks and small sodium peaks. We conclude that intraluminal crystalloids are associated more frequently with low-grade prostatic adenocarcinoma, may occur in benign tissue bordering adenocarcinoma, are predominantly composed of inorganic sulfur, and their presence in benign and atypical prostate biopsies may be of pathologic significance and should warrant further clinical investigation and possibly repeat biopsy.