Objective To develop an evidence-based approach to the diagnostic workup of suspicious upper urinary tract lesions. Methods The PubMed database was searched using the following terms with a filter for English language: upper tract urothelial carcinoma and upper tract transitional cell carcinoma, along with the following corresponding terms: cost, epidemiology, diagnosis ureteroscopy and workup. A total of 404 articles were returned, and 33 were reviewed in full based on relevance. Results Computed tomography urogram is both sensitive and specific (96% and 99%). Cytology is utilized for its specificity (89%-100%). Ureteroscopy and biopsy of an upper tract lesion can be helpful in equivocal cases but can pose challenges in terms of yield and eventual pathologic upstaging. Due to the high sensitivity and specificity of other noninvasive tests, ureteroscopy can be obviated in select cases. We assess the available evidence and devise an algorithm for the evaluation of an upper tract urothelial carcinoma lesion. Conclusion Ureteroscopy can be omitted as part of the diagnostic workup in appropriately selected cases of upper tract urothelial carcinoma.