A retrospective review was conducted of material from 782 transrectal ultrasound-guided prostatic core biopsies to determine whether incidental pieces of rectal mucosa obtained in this manner could harbor clinically significant rectal pathology or incur artifacts that cause diagnostic difficulty. Material from 114 biopsies (14.6%) showed rectal mucosa, and material from 19 (16.7%) showed rectal pathology, including a hyper-plastic polyp in 1, changes consistent with ulcerative proctitis in 8, focal active proctitis in 7, and granulomas in 3. The original pathologist overlooked the hyperplastic polyp. In 1 specimen, rectal lymphocytes and plasma cells that were displaced over prostatic tissue closely mimicked prostatic adenocarcinoma (Gleason score 5). Conversely, in another specimen, prostatic adenocarcinoma (Gleason score 5) that was displaced near rectal mucosa closely mimicked a rectal lymphoid aggregate. Incidental rectal mucosa obtained via transrectal ultrasound-guided prostatic core biopsies occasionally harbors clinically significant rectal pathology and rarely incurs artifacts that cause diagnostic difficulty.