An integrated lab-on-chip capable of performing quantitative polymerase chain reaction (qPCR) is demonstrated in a high-voltage 0.35-μm CMOS process operating at a 3.3 V supply. PCR thermal cycling can be performed by physically moving droplets between three distinct temperature zones on the surface of chip or by thermal cycling a droplet in place. Droplet actuation is enabled by electrowetting-on-dielectric transport at 90 V. On-chip temperature regulation to 0.15°C is performed with on-chip resistive heaters and temperature sensors. PCR cycles are monitored by measuring the fluorescence signal of an intercalator dye using integrated single photon avalanche diodes (SPADs). Results are demonstrated for the recognition of DNA extracts from Staphylococcus aureus (S. aureus) at a detection limit of a few copies per nL target volume.