The Gleason grading system for prostate cancer is a powerful tool that can help choose therapy and predict outcome for patients. The clinical use and problem areas of the Gleason grading system are reviewed. The issues discussed include grade discrepancies between prostate biopsy and resection specimens, grading small foci of tumor, diagnosing and grading cribriform lesions, reporting the grade when 3 grades of cancer are present in a specimen, and assignment of grade when multiple cores of differing grades are present. Finally, differing ways of communicating tumor volume and the percentage of high-grade carcinoma in prostate biopsy cores are considered.