Objective To summarize the clinical experiences for diagnosis and treatment of collecting duct renal cell carcinoma (CDRCC) and to analyze its prognosis. Methods A total of 21 CDRCC patients selected from 6 950 patients with renal cell carcinoma admitted to Changhai Hospital, Changzheng Hospital and Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University (Second Military Medical University) were enrolled in this retrospective study. CDRCC was confirmed by pathological examination. Clinical data, pathological data, imaging data, surgical conditions, postoperative adjuvant treatment and follow-up information of the 21 patients were analyzed. Results The proportion of CDRCC patients was 0.3% (21/6 950). There were 18 males and 3 females, with an average age of (55±13) years. The main symptoms were hematuria and flank pain. Computed tomography showed that the size of the kidney involved was enlarged, the outline of the mass was not smooth, and the boundary of the mass was not clear. After enhancement, the mass was heterogeneously enhanced. The maximum diameter of tumor ranged from 2.4 cm to 8.5 cm, with an average of (5.6±1.7) cm. Lymph node metastases were observed in 5 patients and distant metastasis in 6 patients. TNM clinical stage:8 cases in stage Ⅰ, 2 cases in stage Ⅱ, 5 cases in stage Ⅲ and 6 cases in stage Ⅳ. Twenty patients received surgical treatment, but one did not because of poor general condition. The pathological features of the tumors were grey-white or grey-yellow in section, infiltrating growth, irregular glandular tubular and papillary tissues, some of which had hobnail appearance, interstitial fibrous tissue proliferation and inflammatory cell infiltration. Immunohistochemical staining showed that very low molecular cytokeratin (CAM5.2), tumor-associated epithelial membrane antigen (EMA), paired box gene 8 (PAX8), and cytokeratin 7 (CK7) were positive, while carbonic anhydrase Ⅸ (CAⅨ), proto-oncogene tyrosine-protein kinase kit (C-kit), GATA binding protein 3 (GATA3), neutral endopeptidase (CD10), transformation-related protein 63 (P63), and cytokeratin 20 (CK20) were negative. Sixteen patients were followed up for (33.6±28.9) months on average (range, 4 to 87 months). The median survival time was 39.1 months. One-, two-and five-year survival rate was 71.5%, 57.2%, and 44.5%, respectively. The average survival time of 12 dead patients was (32.2±27.5) months. Conclusion CDRCC is a rare subtype of renal cell carcinoma with short course, rapid progression, high degree of malignancy and poor prognosis. Pathological examination is the golden standard for the diagnosis and surgery is the main treatment at present. Chemotherapy and targeted therapy can be used as adjuvant therapy. Early diagnosis and treatment are the key to a favorable prognosis.