OBJECTIVES: Renal cell carcinoma (RCC) is often found incidentally in asymptomatic individuals undergoing abdominal computed tomography (CT) examinations. The purpose of our study is to develop a deep learning-based algorithm for fully automated detection of small (≤4 cm) RCCs in contrast-enhanced CT images using a multicenter database and to evaluate its performance. MATERIALS AND METHODS: For the algorithmic detection of RCC, we retrospectively selected contrast-enhanced CT images of patients with histologically confirmed single RCC with a tumor diameter of 4 cm or less between January 2005 and May 2020 from 7 centers in the Japan Medical Image Database. A total of 453 patients from 6 centers were selected as dataset A, and 132 patients from 1 center were selected as dataset B. Dataset A was used for training and internal validation. Dataset B was used only for external validation. Nephrogenic phase images of multiphase CT or single-phase postcontrast CT images were used. Our algorithm consisted of 2-step segmentation models, kidney segmentation and tumor segmentation. For internal validation with dataset A, 10-fold cross-validation was applied. For external validation, the models trained with dataset A were tested on dataset B. The detection performance of the models was evaluated using accuracy, sensitivity, specificity, and the area under the curve (AUC). RESULTS: The mean ± SD diameters of RCCs in dataset A and dataset B were 2.67 ± 0.77 cm and 2.64 ± 0.78 cm, respectively. Our algorithm yielded an accuracy, sensitivity, and specificity of 88.3%, 84.3%, and 92.3%, respectively, with dataset A and 87.5%, 84.8%, and 90.2%, respectively, with dataset B. The AUC of the algorithm with dataset A and dataset B was 0.930 and 0.933, respectively. CONCLUSIONS: The proposed deep learning-based algorithm achieved high accuracy, sensitivity, specificity, and AUC for the detection of small RCCs with both internal and external validations, suggesting that this algorithm could contribute to the early detection of small RCCs.