Gains of genetic material or internal rearrangements of chromosome 12p, including 12p overrepresentation or isochromosome 12p [i(12p)], are observed in virtually all germ cell tumors (GCT), in all histologic subtypes, and from various body locations. The chromosomal region involved in these alterations contains the growth and survival promoting oncogene KRAS (12p12.1). Gains or rearrangements of 12p characterize GCT from in situ to chemoresistant stages. Fluorescence in situ hybridization (FISH) detection of chromosome 12p anomalies is a sensitive and specific test for the diagnosis of germ cell tumors. Here we provide a detailed protocol for FISH detection of isochromosome 12p and chromosome 12p overrepresentation. The method is helpful for diagnosis of germ cell origin, and for selection of patients who may benefit from cisplatin-based chemotherapy.