This paper presents an automatic mitosis detection approach of histopathology slide imaging based on using neutrosophic sets (NS) and moth-flame optimization (MFO). The proposed approach consists of two main phases, namely candidate’s extraction and candidate’s classification phase. At candidate’s extraction phase, Gaussian filter was applied to the histopathological slide image and the enhanced image was mapped into the NS domain. Then, morphological operations have been implemented to the truth subset image for more enhancements and focus on mitosis cells. At candidate’s classification phase, several features based on statistical, shape, texture and energy features were extracted from each candidate. Then, a principle of the meta-heuristic MFO algorithm was adopted to select the best discriminating features of mitosis cells. Finally, the selected features were used to feed the classification and regression tree (CART). A benchmark dataset consists of 50 histopathological images was adopted to evaluate the performance of the proposed approach. The adopted dataset consists of five distinct breast pathology slides. These slides were stained with H&E acquired by Aperio XT scanners with 40-x magnification. The total number of mitoses in 50 database images is 300, which were annotated by an expert pathologist. Experimental results reveal the capability of the MFO feature selection algorithm for finding the optimal feature subset which maximizing the classification performance compared to well-known and other meta-heuristic feature selection algorithms. Also, the high obtained value of accuracy, recall, precision and f-score for the adopted dataset prove the robustness of the proposed mitosis detection and classification approach. It achieved overall 65.42 % f-score, 66.03 % recall, 65.73 % precision and accuracy 92.99 %. The experimental results show that the proposed approach is fast, robust, efficient and coherent. Moreover, it could be used for further early diagnostic suspicion of breast cancer.