Histopathological grading of cancer is a measure of the cell appearance in malignant neoplasms. Grading offers an in-sight to the growth of the cancer and helps in developing individual treatment plans. The Nottingham grading system [12], well known method for invasive breast cancer grading, primarily relies on the mitosis count in histopathological slides. Pathologists manually identify mitotic figures from a few thousand slide images for each patient to determine the grade of the cancer. Mitotic figures are hard to identify as the appearance of the mitotic cells change at different phases of mitosis. So, the manual cancer grading is not only a tedious job but also prone to observer variability. We propose a fast and accurate approach for automatic mitosis detection from histopathological images using an enhanced random forest classifier with weighted random trees. The random trees are assigned a tree penalty and a forest penalty depending on their classification performance at the training phase. The weight of a tree is calculated based on these penalties. The forest is trained through regeneration of population from weighted trees. The input data is classified based on weighted voting from the random trees after several populations. Experiments show at least 11 percent improvement in F1 score on more than 450 histopathological images at ×40 magnification. Copyright 2014 ACM.