When the mutation affects the melanocytes of the body, a condition called melanoma results which is one of the deadliest skin cancers. Early detection of cutaneous melanoma is vital for raising the chances of survival. Melanoma can be due to inherited defective genes or due to environmental factors such as excessive sun exposure. The accuracy of the state-of-the-art computer-aided diagnosis systems is unsatisfactory. Moreover, the major drawback of medical imaging is the shortage of labeled data. Generalized classifiers are required to diagnose melanoma to avoid overfitting the dataset. To address these issues, blending ensemble-based deep learning (BEDLM-CMS) model is proposed to detect mutation of cutaneous melanoma by integrating long short-term memory (LSTM), Bi-directional LSTM (BLSTM) and gated recurrent unit (GRU) architectures. The dataset used in the proposed study contains 2608 human samples and 6778 mutations in total along with 75 types of genes. The most prominent genes that function as biomarkers for early diagnosis and prognosis are utilized. Multiple extraction techniques are used in this study to extract the most-prominent features. Afterwards, we applied different DL models optimized through grid search technique to diagnose melanoma. The validity of the results is confirmed using several techniques, including tenfold cross validation (10-FCVT), independent set (IST), and self-consistency (SCT). For validation of the results multiple metrics are used which include accuracy, specificity, sensitivity, and Matthews’s correlation coefficient. BEDLM gives the highest accuracy of 97% in the independent set test whereas in self-consistency test and tenfold cross validation test it gives 94% and 93% accuracy, respectively. Accuracy of in self-consistency test, independent set test, and tenfold cross validation test is LSTM (96%, 94%, 92%), GRU (93%, 94%, 91%), and BLSTM (99%, 98%, 93%), respectively. The findings demonstrate that the proposed BEDLM-CMS can be used effectively applied for early diagnosis and treatment efficacy evaluation of cutaneous melanoma.