Deep learning fostered a leap ahead in automated skin lesion analysis in the last two years. Those models, however, are expensive to train and difficult to parameterize. Objective: We investigate methodological issues for designing and evaluating deep learning models for skin lesion analysis. We explore ten choices faced by researchers: use of transfer learning, model architecture, train dataset, image resolution, type of data augmentation, input normalization, use of segmentation, duration of training, additional use of Support Vector Machines, and test data augmentation. Methods: We perform two full factorial experiment, for five different test datasets, resulting in 2560 exhaustive trials in our main experiment, and 1280 trials in our assessment of transfer learning. We analyze both with multi-way analyses of variance (ANOVA). We use the exhaustive trials to simulate sequential decisions and ensembles, with and without the use of privileged information from the test set. Results — main experiment: Amount of train data has disproportionate influence, explaining almost half the variation in performance. Of the other factors, test data augmentation and input resolution are the most influential. Deeper models, when combined, with extra data, also help. — transfer experiment: Transfer learning is critical, its absence brings huge performance penalties. — simulations: Ensembles of models are the best option to provide reliable results with limited resources, without using privileged information and sacrificing methodological rigor. Conclusions and Significance: Advancing research on automated skin lesion analysis requires curating larger public datasets. Indirect use of privileged information from the test set to design the models is a subtle, but frequent methodological mistake that leads to overoptimistic results. Ensembles of models are a cost-effective alternative to the expensive full-factorial and to the unstable sequential designs.