<p>Due to the lack of efficient mpox diagnostic technology, mpox cases continue to increase. Recently, the great potential of deep learning models in detecting mpox and non-mpox has been proven. However, existing methods are susceptible to interference from various noises in real-world settings, require diverse non-mpox images, and fail to detect abnormal input, which makes them unsuitable for practical deployment and application. To address these challenges, we proposed a novel strategy based on image inpainting called “Mask, Inpainting, and Measure” (MIM). In MIM’s pipeline, a generative adversarial network learns feature representations of mpox images by inpainting the masked mpox images. On this basis, MIM measure the similarity between the inpainted image and the original image to detect mpox and non-mpox. Compared with multi-class classification models, MIM can handle unknown categories and abnormal inputs more effectively. We used the recognized mpox dataset (MSLD) and a dataset containing 18 categories of non-mpox skin diseases to verify the effectiveness and robustness of MIM. Experimental results show that the average AUROC of MIM achieves 0.8237. In addition, external clinical testing further demonstrates the robustness of MIM. Importantly, we developed a free smartphone app to help the public and healthcare professionals detect mpox more conveniently.</p>