Single-stranded nucleic acid molecules that are complementary to each other will form hybrids under appropriate conditions. Hybridization tests make use of this phenomenon and employ labeled molecules called probes to detect specific complementary molecules called targets. Nucleic acid hybridization is the most sensitive method for detecting HPV in clinical specimens and the only one capable of identifying specific HPV types. There are many alternative hybridization test formats; most of them use either filters or glass slides as solid supports. Of the established tests, Southern blot hybridization remains the most sensitive and specific test for HPV DNA but has the drawback of also being the most time consuming. Several novel methods show promise, and some innovative procedure may eventually dominate routine nucleic acid detection. The ideal test would be simple enough to permit automation.