Molecular techniques are increasingly being employed in the field of dermatology, helping to facilitate the diagnosis and prognostication of a variety of skin diseases, in addition to guiding the selection of appropriate treatment, monitoring of therapy and identification of novel therapeutic targets. A basic knowledge of the principles of molecular diagnostics is now essential for physicians involved in the diagnosis and/or treatment of skin diseases, primarily dermatopathologists and dermatologists. Essentially, molecular diagnostic testing involves the analysis of nucleic acids (DNA and/or RNA) with a wide variety of laboratory methods. Nucleic acid amplification methods have traditionally dominated this field, with the most readily recognizable of these being polymerase chain reaction (PCR). Newer technologies are now being incorporated and can facilitate parallel gene analyses (i.e.,cDNA/oligonucleotide microarrays) and/or correlation of genomic changes with morphological features of disease [i.e., fluorescence in situ hybridization (FISH)]. This discussion provides an overview of the principles of molecular technologies most frequently used in dermatology and highlights their applications in particular disease categories.