The development of new therapeutic options for renal tumors has lead to the need of a pretherapeutic diagnosis for an increasing proportion of patients presenting with a renal mass. This need is particularly important for a small, incidentally discovered renal mass (less than 4 cm) as it can be a benign lesion in a significant percentage of cases. Recent studies have shown that needle biopsy is an accurate and safe method allowing for a precise histopathological diagnosis of the mass in most cases. The aims of the biopsy are (1) to assess the benign or malignant nature of the lesion, (2) to assess the primary or secondary nature of the lesion, and (3), in case of a primary malignancy, to determine histological prognostic factors, such as the tumor type. This review, based on the most recent literature and our own experience, is intended to provide a practical approach to the diagnosis, relying on appropriate morphologic assessment and the use of immunohistochemistry.