RATIONALE AND OBJECTIVES: We propose a novel convolutional neural network derived pixel-wise breast cancer risk model using mammographic dataset. MATERIALS AND METHODS: An institutional review board approved retrospective case-control study of 1474 mammographic images was performed in average risk women. First, 210 patients with new incidence of breast cancer were identified. Mammograms from these patients prior to developing breast cancer were identified and made up the case group [420 bilateral craniocaudal mammograms]. The control group consisted of 527 patients without breast cancer from the same time period. Prior mammograms from these patients made up the control group [1054 bilateral craniocaudal mammograms]. A convolutional neural network (CNN) architecture was designed for pixel-wise breast cancer risk prediction. Briefly, each mammogram was normalized as a map of z-scores and resized to an input image size of 256 × 256. Then a contracting and expanding fully convolutional CNN architecture was composed entirely of 3 × 3 convolutions, a total of four strided convolutions instead of pooling layers, and symmetric residual connections. L2 regularization and augmentation methods were implemented to prevent overfitting. Cases were separated into training (80%) and test sets (20%). A 5-fold cross validation was performed. Software code was written in Python using the TensorFlow module on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. RESULTS: The average age of patients between the case and the control groups was not statistically different [case: 57.4years (SD, 10.4) and control: 58.2years (SD, 10.9), p = 0.33]. Breast Density (BD) was significantly higher in the case group [2.39 (SD, 0.7)] than the control group [1.98 (SD, 0.75), p < 0.0001]. On multivariate logistic regression analysis, both CNN pixel-wise mammographic risk model and BD were significant independent predictors of breast cancer risk (p < 0.0001). The CNN risk model showed greater predictive potential [OR = 4.42 (95% CI, 3.4-5.7] compared to BD [OR = 1.67 (95% CI, 1.4-1.9). The CNN risk model achieved an overall accuracy of 72% (95%CI, 69.8-74.4) in predicting patients in the case group. CONCLUSION: Novel pixel-wise mammographic breast evaluation using a CNN architecture can stratify breast cancer risk, independent of the BD. Larger dataset will likely improve our model.