Immunohistochemical stains (IHC) stains for high molecular weight cytokeratin (HMWCK) may show the presence or absence of basal cells in a small focus of atypical glands helping to establish a benign or malignant diagnosis respectively. From January 1994 to the present, we have generated intervening unstained slides on all prostate needle biopsies for potential IHC stains for HMWCK because lesions may not survive deeper sectioning into the block. Of 1105 prostate needle biopsy cases seen at Johns Hopkins from January 1994 to December 1996, IHC staining for HMWCK was initially done on 94 (8.5%). To see whether lesions would still have been present for evaluation if we did not have intervening slides, we repeated the IHC stains for HMWCK off the paraffin blocks in 74 cases for which material was available for study. Care was taken not to trim the blocks. In 52 cases, the original HMWCK helped to establish a diagnosis; in 31 of these cases the lesion was not present on repeat IHC stains from the block. Of these 31 cases, the original HMWCK from intervening unstained slides helped to establish cancer (n = 23) or a benign (n = 8) diagnosis. The use of intervening unstained slides was critical to establish a diagnosis in 31 (2.8%) of 1105 prostate needle biopsies and saved the cost of repeat biopsy ($68,200) and spared these patients from a second surgical procedure.