Prostate biopsy is the gold standard for diagnosing prostate cancer and reliable pathological assessment is essential for guiding management. Research efforts over the past few years have aimed to establish a more universal approach to management according to pathological grading; however, high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands suspicious for carcinoma are two diagnoses without standardized follow-up and treatment pathways. Much of this uncertainty is due to limited evidence describing the subsequent rates of cancer and high-grade cancer when HGPIN or atypical glands are detected on initial biopsy. Fortunately, data from the past decade have shed light on these phenomena, and an improved understanding of the implications of the presence of HGPIN and atypical glands on prostate biopsy means that clinical recommendations can be made for the management of patients with these diagnoses.