We evaluate the reliability of routine sextant prostate biopsy to detect unilateral lesions. A total of 365 men with complete records including all clinical and pathologic variables who underwent a preoperative sextant biopsy and subsequent radical prostatectomy (RP) for clinically localized prostate cancer at our medical center between January 1996 and December 2006 were identified. When the sextant biopsy detects unilateral disease, according to RP results, the NPV is high (91%) with a low false negative rate (9%). However, the sextant biopsy has a PPV of 28% with a high false positive rate (72%). Therefore, a routine sextant prostate biopsy cannot provide reliable, accurate information about the unilaterality of tumor lesion(s).