Abstract : High-content imaging is an emerging technology for the analysis and quantification of biological phenomena. Thus, classifying a huge number of cells or quantifying markers from large sets of images by experts is a very time-consuming and poorly reproducible task. In order to overcome such limitations, we propose a supervised method for automatic cell classification. Our approach consists of two steps: the first one is an indexing stage based on specific bio-inspired features relying on the distribution of contrast information on segmented cells. The second one is a supervised learning stage that selects the prototypical samples best representing the cell categories. These prototypes are used in a leveraged k-NN framework to predict the class of unlabeled cells. In this paper we have tested our new learning algorithm on cellular images acquired for the analysis of pathologies. In order to evaluate the automatic classification performances, we tested our algorithm on the HEp2 Cells dataset of (Foggia et al, CBMS 2010). Results are very promising, showing classification precision larger than 96% on average, thus suggesting our method as a valuable decision-support tool in such cellular imaging applications.