Objective: Medical coding is used to identify and standardize clinical concepts in the records collected from healthcare services. The tenth revision of the International Classification of Diseases (ICD-10) is the most widely-used coding with more than 11,000 different diagnoses, affecting research, reporting, and funding. Unfortunately, ICD-10 code sets tend to follow biased, unbalanced, and scattered distributions. These distribution attributes, along with high lexical variability, severely restrict performance when coded clinical records are used to infer code sets in uncoded records. To improve that inference, we explore a combination of example-based methods optimized to capture codes with different appearance frequencies in data sets. Materials and Methods: The proposed exploration has been carried out on Spanish hospital discharge reports coded by experts, excluding all sentences without any biomedical concept. Representations based on semantic and lexical features are explored, using both global and labelspecific attributes. In turn, algorithms based on binary outputs, groups of subsets and extreme classification are compared. Lists of codes together with their confidence values (certainty probabilities) are suggested by each method. Results: Diverse spectral behaviors are shown for each method. Binary classifiers seem to maximize the capture of more popular codes, while extreme classifiers promote infrequent ones. In order to exploit such differences, ensemble approaches are proposed by weighting every output code according to the method, confidence value and appearance frequency. The rule-based combination reaches a 46% Precision at 10 (P@10), which means a 15% improvement over the best individual proposal. Conclusion: Assembling methods based on weighting each code according to training frequency and performance can achieve better overall Precision scores on extreme distributions, such as ICD-10 coding. INDEX TERMS Extreme classification, XMTC, ICD-10 coding, text mining.