Individual cells are prepared from histological tissue sections of routinely formalin-fixed and paraffin-embedded tissues using an ultraviolet laser micromanipulator. This technology, in combination with polymerase chain reaction (PCR)-based gene analysis, will enable researchers to routinely detect a variety of nucleic acid abnormalities underlying cancer, infection, and genetic disease with previously unknown sensitivity: at the single cell level. The utility of this technique is demonstrated by PCR amplification and sequencing of the E-cadherin gene, which codes for a homophilic cell-to-cell adhesion molecule, in early gastric carcinomas of the diffuse type of Lauren's classification. The main characteristics of the laser-assisted microdissection technique are high precision without contamination and easy application. The assignment of individual gene sequences to single cells will now provide a direct link between molecular biology on the one hand and histology and pathology on the other.