Background: Although the use of PC-RPLND in testis cancer patients in the salvage setting has been reported, existing data characterizing histologic findings are poor. Methods: 179 PC-RPLNDs after salvage chemotherapy were selected from a prospective database of 504 RTRs (434 patients, 2003-2018). Uni- and multivariate analyses were used to assess the impact of preoperative positive markers, residual diameter, and type of salvage chemotherapy (either conventional salvage [CTX] or high dose chemotherapy [HDC]) on vital cancer histology (including teratoma with malignant transformation) at PC-RPLND. Results: Median age was 37 years (IQR 30-45). 11.5% of patients underwent thoraco-abdominal PC-RPLND and adjunctive surgeries were needed in 41.7%. Clavien-Dindo > II complications were registered in 5% of cases. After stratification for CTX and HDC, AFP only, β-HCG only, and both markers elevated were seen in 27.8%, 7.8%, and 2.2%, and 33%, 18.2% and 5.7% of patients, respectively. Overall, necrosis, postpubertal teratoma, and vital cancer were found in 30%, 29%, and 42%, respectively. Vital cancer was found in residual tumor sizes of < 2 cm and ≥ 2 cm in 41.2% and 32.9%, respectively. After stratification for CTX and HDC, patients after CTX had lower rates of necrosis (26% vs. 34%, p = 0.2) but not of vital cancer (42% vs. 42%, p = 0.9). The predictors of vital cancer were represented by the presence of AFP elevation only (OR 4.7, p = 0.001) and both markers elevated (OR 8.6, p = 0.02). Conclusions: In the salvage setting, the rate of vital cancer in residual tumor is three times higher as compared to the first-line setting. Presence of AFP elevation only or both markers elevated represent predictors of vital cancer. PC-RPLND has to be performed after salvage chemotherapy independent of the residual tumor diameter.