Germ cell neoplasia in situ (GCNIS) is the precursor of both seminomatous and non-seminomatous TGCTs. ¹ From a developmental perspective, GCNIS is thought to originate in reprogrammed gonocytes. ² Patients with disorders of sex development (DSD), history of cryptorchidism or a prior germ cell tumor, and family history of TGCT demonstrate a higher risk of developing GCNIS and post-pubertal TGCTs. ^3-5 With some important exceptions (e.g., teratoma), post-pubertal TGCTs are exquisitely sensitive to platinum-based chemotherapy, and most seminomas are also radiosensitive. ⁶ For clinical management and treatment purposes, post-pubertal TGCTs derived from GCNIS are divided into seminomas and non-seminomas (which includes mixed germ cell tumors that may include a component of seminoma). GCNIS-derived TGCTs demonstrate a polyploid genome as a consequence of early whole genome doubling (WGD) events. ⁷ Loss of chromosomal arms and entire chromosomes are recurrent and characteristic of each sub-category (i.e., seminomatous and non-seminomatous TGCTs). TGCTs demonstrate one of the lowest mutational burdens among human cancers, with kinase mutations identified in a relatively minor subset (most notably KIT, KRAS and NRAS). ⁷ The hallmark of GCNIS-derived TGCTs, i(12p), is thought to represent a late event that likely drives the transition from GCNIS [i(12p)-negative] to invasive TGCT [i(12p)-positive)]. ^7,8