"Sarcomas" in patients with testicular germ cell tumors (GCTs) are a common form of "somatic-type malignancy." There is support, based on morphology and immunohistochemistry, that many such sarcomatous tumors represent an unusual form of yolk sac tumor (YST). A virtually universal chromosomal anomaly in GCTs is increase in 12p copy number, often in the form of isochromosome 12p [i(12p)], but this aspect of sarcomatoid YSTs has not hitherto been studied. We performed interphase fluorescent in situ hybridization assay for detection of increased 12p copy number in sarcomatoid YSTs using a bacterial artificial chromosome-derived probe localized to 12p12.1 and a commercially available centromeric probe. Sixteen formalin-fixed, paraffin-embedded specimens from 11 patients, along with normal controls, were studied. Overrepresentation of 12p was expressed as a ratio between the number of signals for 12p and the number of signals for centromere 12. A ratio ≥1.3 was considered overrepresentation. All cases were postchemotherapy recurrences or metastases. Ages ranged 22 to 38 years (mean: 36). Most tumors (12/16) showed myxoid or fibromyxoid stroma and 15 of 16 were high grade. Thirteen of 16 specimens (81%) showed overrepresentation of 12p by the above criteria. Two cases exhibited loss of 12p and 1 case had gain of a whole chromosome 12 (trisomy 12). We conclude that, as in other GCTs, sarcomatous differentiation of YST demonstrates 12p alterations that can be identified by interphase fluorescent in situ hybridization. Apart from 12p overrepresentation, these tumors may exhibit loss of 12p or even gain of an entire chromosome 12 (trisomy 12). Increase in 12p copy number of a sarcomatous neoplasm provides support for sarcomatoid YST in clinically ambiguous settings.