The purpose of this study was to evaluate the utility of Semaphorin-3A (Sema-3A) as a biomarker for diagnosis and management of upper tract urothelial carcinoma, independently and in conjunction to cytology. Upper tract noninvasive urothelial carcinoma is a lifelong chronic non-curable disease. It is infamously difficult both to diagnose and to follow-up, and current non-invasive methods are commonly inadequate. Sema-3A protein levels can be measured from a simple urine test and can aid in the diagnosis and follow-up and early non-invasive tumor recurrence detection. Assigned cases for this series were those with pathologically verified upper tract neoplastic lesions. Urine samples for cytology and Sema-3A were taken on admission from all recruited patients. Sema-3A protein levels were determined using ELISA in every sample, and the tumor was graded and staged according to the 2004 WHO grading system. Descriptive and statistical analysis was performed to evaluate the performance of Sema-3A and the cytology exam. This case series included 10 patients with pathologically proven upper tract urothelial carcinoma. Sensitivity for recognizing disease was calculated as 80% for cytology, and 89% for a predetermined Sema-3A cutoff. Combining the strengths of both urine tests to a single criterion (Sema-3A ＞ 5 or positive cytology) resulted in 100% sensitivity. In conclusion, in the current preliminary study, high levels of Sema-3A correlated with upper-tract urothelial cancer stage and displayed higher sensitivity than cytology. Combined analysis of both positive Sema-3A and cytology demonstrated 100% sensitivity. Thus, Sema-3A levels can potentially serve as a reliable biomarker for diagnosis and management for the disease, given that further dedicated studies with larger patient cohorts are undertaken.