Metastatic germ cell tumors are highly chemo-sensitive with cure rates as high as 90-95% for good-risk disease, 75% with intermediate risk disease and 40-50% with poor-risk disease. Serum markers hCG or AFP are of pivotal importance in management and prognosis of patients with germ cell tumors and increased levels during chemotherapy are thought to represent viable residual disease. A significant rise would seem to imply futility in continuing the same salvage chemotherapy regimen. Tumor marker rise at initiation of second course or within first week of second course of HDCE is also assumed to reflect a poor prognosis. To the best of our knowledge, there has been no published data on the incidence and significance of tumor marker rise during initiation of second course of HDCE. In this study, we have retrospectively analyzed the frequency and outcome of rising tumor marker at start of or within 1 week of initiation of second course of HDCE. Tumor marker rise during second course of HDCE is uncommon. Although it represents an adverse prognostic variable, cure is still possible with institution of second course of HDCE.