The automated assessment of tumors in medical image analysis encounters challenges due to the resemblance of colon and lung tumors to non-mitotic nuclei and their heteromorphic characteristics. An accurate assessment of tumor nuclei presence is crucial for determining tumor aggressiveness and grading. This paper proposes a new method called ColonNet, a heteromorphous convolutional neural network (CNN) with a feature grafting methodology categorically configured for analyzing mitotic nuclei in colon and lung histopathology images. The ColonNet model consists of two stages: first, identifying potential mitotic patches within the histopathological imaging areas, and second, categorizing these patches into squamous cell carcinomas, adenocarcinomas (lung), benign (lung), benign (colon), and adenocarcinomas (colon) based on the model’s guidelines. We develop and employ our deep CNNs, each capturing distinct structural, textural, and morphological properties of tumor nuclei, to construct the heteromorphous deep CNN. The execution of the proposed ColonNet model is analyzed by its comparison with state-of-the-art CNNs. The results demonstrate that our model surpasses others on the test set, achieving an impressive F1 score of 0.96, sensitivity and specificity of 0.95, and an area under the accuracy curve of 0.95. These outcomes underscore our hybrid model’s superior performance, excellent generalization, and accuracy, highlighting its potential as a valuable tool to support pathologists in diagnostic activities.