Prostatic carcinoma is increasingly diagnosed on small foci of core needle biopsy specimens. What constitutes adequate sampling of this tissue has not been investigated. Two hundred twenty-nine cases were reviewed, which included 47 cores with atypical foci, 22 with high-grade prostatic intraepithelial neoplasia (PIN), and 533 diagnostic of carcinoma. Six core specimens were obtained for each case, and two blocks were prepared containing three cores each. At least three slides containing multiple serial sections were prepared from each block. Ninety-seven percent of atypical foci, 0% of high-grade PIN foci, and 25% of carcinomatous foci comprised less than 5% of the tissue in the core and measured less than 1 mm in greatest dimension. Thirteen percent of atypical foci, 0% of high-grade PIN foci, and 3% of carcinomatous foci were not present on the first slide. In every case, the tissue containing the focus was not present on the first slide. Thirteen percent of atypical foci and 3% of carcinomatous foci are not present on the first slide of prostate core needle biopsy specimens because the tissue containing these foci simply is not cut. As proposed in this report, at least three slides are necessary to detect all lesions.