A program storage device is provided readable by machine, tangibly embodying a program of instructions executable by the machine to perform method steps for classification of biological tissue by gene expression profiling. The method steps include providing a training set of gene expression profiles of known tissue samples, providing a first-layer strong classifier of the known tissue samples by combining weak classifiers using boosting, creating two sample sets based on the first classifier, populating the two sample sets with a next-layer of classifiers based on a previous-layer classifier, organizing the classifiers in a tree data structure, and outputting the tree data structure as a probabilistic boosting tree classifier for tissue sample classification and disease subtype discovery. A multi-class diagnosis problem is transformed to a two-class diagnosis process by finding an optimal feature and dividing the multi-class problem into two-classes.