Background Deep neural networks are showing impressive results in different medical image classification tasks. However, for real-world applications, there is a need to estimate the network’s uncertainty together with its prediction. Objective In this review, we investigate in what form uncertainty estimation has been applied to the task of medical image classification. We also investigate which metrics are used to describe the effectiveness of the applied uncertainty estimation Methods Google Scholar, PubMed, IEEE Xplore, and ScienceDirect were screened for peer-reviewed studies, published between 2016 and 2021, that deal with uncertainty estimation in medical image classification. The search terms “uncertainty,” “uncertainty estimation,” “network calibration,” and “out-of-distribution detection” were used in combination with the terms “medical images,” “medical image analysis,” and “medical image classification.” Results A total of 22 papers were chosen for detailed analysis through the systematic review process. This paper provides a table for a systematic comparison of the included works with respect to the applied method for estimating the uncertainty. Conclusions The applied methods for estimating uncertainties are diverse, but the sampling-based methods Monte-Carlo Dropout and Deep Ensembles are used most frequently. We concluded that future works can investigate the benefits of uncertainty estimation in collaborative settings of artificial intelligence systems and human experts. International Registered Report Identifier (IRRID) RR2-10.2196/11936