Renal cell neoplasms are a heterogeneous group of tumours in terms of pathological features and prognostic behaviour. The genetics of these tumours may aid in correct diagnosis and accurate assessment of prognosis. In ambiguous cases it may be necessary to utilise new markers that are capable of further discerning renal cell neoplasms. Fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue is an increasingly useful technique in the detection of many diagnostic chromosomal abnormalities, among which chromosomes 1, 2, 3p, 6, 7, 10, 17 and Y are the most common. The addition of FISH to histological evaluation improves the diagnostic accuracy of core biopsies from renal masses, which may have an important impact in clinical management of many cases due to newer therapeutic approaches, including cryo- or radiofrequency ablation, nephron-sparing surgeries and target therapies.