We propose in this article a content-based image retrieval (CBIR) method for diagnosis aid in medical fields. In the proposed system, images are indexed in a generic fashion, without extracting domain-specific features: a signature is built for each image from its wavelet transform. These image signatures characterize the distribution of wavelet coefficients in each subband of the decomposition. A distance measure is then defined to compare two image signatures and thus retrieve the most similar images in a database when a query image is submitted by a physician. To retrieve relevant images from a medical database, the signatures and the distance measure must be related to the medical interpretation of images. As a consequence, we introduce several degrees of freedom in the system so that it can be tuned to any pathology and image modality. In particular, we propose to adapt the wavelet basis, within the lifting scheme framework, and to use a custom decomposition scheme. Weights are also introduced between subbands. All these parameters are tuned by an optimization procedure, using the medical grading of each image in the database to define a performance measure. The system is assessed on two medical image databases: one for diabetic retinopathy follow up and one for screening mammography, as well as a general purpose database. Results are promising: a mean precision of 56.50%, 70.91% and 96.10% is achieved for these three databases, when five images are returned by the system.