OBJECTIVES:: The prognosis for upper urinary tract urothelial carcinoma is generally poorer than that for bladder cancer, and prognostic predictors with a high specificity for upper urinary tract urothelial carcinoma (UUT-UC) are needed to optimize treatment. In fact, the only preoperative predictor currently available is C-reactive protein. In the present study, we investigated the usefulness of pretreatment serum CYFRA 21–1 as a new prognostic predictor in UUT-UC. METHODS:: A total of 45 UUT-UC patients for whom serum CYFRA 21–1 was measured before treatment were included in this retrospective analysis. Patients were separated into high and low serum CYFRA 21–1 groups based on a cut-off value of 2.7 ng/mL determined from a receiver operating characteristic curve. Kaplan–Meier survival curves were calculated and the overall survival rate was statistically analyzed for the high and low pretreatment serum CYFRA 21–1 groups using the log–rank test. Multivariable analysis was carried out using the Cox proportional hazards analysis. RESULTS:: By the median follow-up period of 14.4 months, 20 patients (44.4%) had died. Of the 45 patients, 23 (51.1%) were in the high pretreatment serum CYFRA 21–1 group, and the overall survival rate of this group was significantly lower (P < 0.001). Multivariable analysis identified only distant metastasis (P < 0.001) and pretreatment serum CYFRA 21–1 (P = 0.039) as independent prognostic predictors. Distant metastasis did not significantly differ between the two groups or correlate with pretreatment serum CYFRA 21–1. CONCLUSION:: These findings suggest that pretreatment serum CYFRA 21–1 values could serve as a prognostic predictor of UUT-UC.