We present a method for automatic generation of DNA microarray probe sets. This approach is well suited particularly for specificity evaluation of designed probes in large data sets. Algorithms for probe preselection, hybridization prediction and probe selection are presented. Combinatorial techniques are introduced for selecting probe sets of high differentiation capability even from conserved gene sequences, for instance automatic generation of group specific probes and excluding probes. A basic prototype was implemented including a shared memory parallelization and distribution. The principal applicability of our method to a database of very conserved sequence data was shown and the run-time performance estimated.