We have developed a microbiopsy platform as a technology that can enable repeated, minimally invasive sampling without the need of local anesthesia and without pain and scarring - while providing enough tissue for molecular detection of disease and live-cell assays. Herein we demonstrated the benefit of targeting capability built in the device enable precise tissue sampling within melanocytic skin micro-lesions. We have showed that unguided microbiopsy sampling has a targeting spread of 0.29 ± 0.32 (x) by 1.05 ± 0.56 (y) mm from the center of interest. Targeting spread was reduced by 4.8 (horizontal) and 1.6 (vertical) fold when an in-house target cassette was coupled to the device. We evaluated this device in a man in his 50s. He had Fitzpatrick skin type II and MC1R wildtype genotype. The volunteer presented with a suspicious pigmented lesion. The lesion was excised and sub-millimetre targeted microbiopsies taken from the 3 morphologically distinct regions of the nevus for molecular analysis. An evolving melanoma in situ was found to be growing from within a dysplastic nevus. The BRAF and NRAS mutation status will be discussed.