The aim of this study was to investigate the usefulness of topical provocation in the diagnosis of metamizol- and naproxen-induced fixed drug eruption (FDE). Five patients with metamizol- and four patients with naproxen-induced FDE established by oral provocation were tested with the causative drugs at concentrations of 10%, 20%, and 50% in white petrolatum both on previously involved and uninvolved skin using the occlusive patch test technique. Additionally, four patients with metamizol- and five patients with naproxen-induced FDE, and 20 healthy controls were tested openly with drug preparations in dimethyl sulfoxide (DMSO). Tape-stripping occlusive patch testing in petrolatum remained negative in all. Open testing with drug preparations in DMSO revealed positive results in all four patients tested with metamizol mainly at concentrations of 20%, and in three of five patients tested with naproxen exclusively at concentrations of 50%. No positive reaction was seen on previously uninvolved skin and in healthy controls with any drug concentration and pure DMSO. In conclusion, repeated open testing with concentrations of the drugs up to 50% in DMSO seems to be a reliable test method in metamizol-induced FDE whereas oral provocation is still the most reliable method for naproxen-induced FDE as false negative results were common when testing topically with naproxen.