There is no clinical tool available to primary care physicians or dermatologists that could provide objective identification of suspicious skin cancer lesions. Multispectral autofluorescence lifetime imaging (maFLIM) dermoscopy enables label-free biochemical and metabolic imaging of skin lesions. This study investigated the use of pixel-level maFLIM dermoscopy features for objective discrimination of malignant from visually similar benign pigmented skin lesions. Clinical maFLIM dermoscopy images were acquired from 60 pigmented skin lesions before undergoing a biopsy examination. Random forest and deep neural networks classification models were explored, as they do not require explicit feature selection. Feature pools with either spectral intensity or bi-exponential maFLIM features, and a combined feature pool, were independently evaluated with each classification model. A rigorous cross-validation strategy tailored for small-size datasets was adopted to estimate classification performance. Time-resolved bi-exponential autofluorescence features were found to be critical for accurate detection of malignant pigmented skin lesions. The deep neural network model produced the best lesion-level classification, with sensitivity and specificity of 76.84%±12.49% and 78.29%±5.50%, respectively, while the random forest classifier produced sensitivity and specificity of 74.73%±14.66% and 76.83%±9.58%, respectively. Results from this study indicate that machine-learning driven maFLIM dermoscopy has the potential to assist doctors with identifying patients in real need of biopsy examination, thus facilitating early detection while reducing the rate of unnecessary biopsies.