Microarray technology uses the sequence dependent hybridization (binding) affinity of surface-bound oligonucleotide strands for the quantification of complex nucleic acid mixtures. In spite of its huge potential in life science and medicine, microarray oligonucleotide hybridization remains far from being understood. Taking advantage of microarray combinatorial possibilities we show that, although surface bound, the hybridization affinities of single-base mismatched oligonucleotides can be derived from first principles using parameters from bulk.