The aim of this study was to associate and predict B-rapidly accelerated fibrosarcoma valine 600 (BRAFV600) mutation status with both conventional and radiomics 18F-FDG PET/CT features, while exploring several methods of feature selection in melanoma radiomics. Methods: Seventy unresectable stage III–IV melanoma patients who underwent a baseline 18F-FDG PET/CT scan were identified. Patients were assigned to the BRAFV600 group or BRAF wild-type group according to mutational status. 18F-FDG uptake quantification was performed by semiautomatic lesion delineation. Four hundred eighty radiomics features and 4 conventional PET features (SUVmax, SUVmean, SUVpeak, and total lesion glycolysis) were extracted per lesion. Six different methods of feature selection were implemented, and 10-fold cross-validated predictive models were built for each. Model performances were evaluated with areas under the curve (AUCs) for the receiver operating characteristic curves. Results: Thirty-five BRAFV600 mutated patients (100 lesions) and 35 BRAF wild-type patients (79 lesions) were analyzed. AUCs predicting the BRAFV600 mutation varied from 0.54 to 0.62 and were susceptible to feature selection method. The best AUCs were achieved by feature selection based on literature, a penalized binary logistic regression model, and random forest model. No significant difference was found between the BRAFV600 and BRAF wild-type group in conventional PET features or predictive value. Conclusion: BRAFV600 mutation status is not associated with, nor can it be predicted with, conventional PET features, whereas radiomics features were of low predictive value (AUC 5 0.62). We showed feature selection methods to influence predictive model performance, describing and evaluating 6 unique methods. Detecting BRAFV600 status in melanoma based on 18F-FDG PET/CT alone does not yet provide clinically relevant knowledge.