Picolinamide is a heterocyclic compound derived from picolinic acid that has attracted interest for potential use in cosmetic formulations due to its physicochemical stability and biological activity. Currently, no specific maximum concentration limit has been established for picolinamide under Korean cosmetic regulations. As no data are available regarding the dermal absorption of picolinamide in cosmetic products, an in vitro dermal absorption study was conducted in accordance with the guidelines of the Ministry of Food and Drug Safety (MFDS) of Korea. Prior to the dermal absorption study, an analytical method was established using liquid chromatography–tandem mass spectrometry (LC–MS/MS) with a multiple reaction monitoring (MRM) technique to quantify picolinamide in various matrices, including swabs, stratum corneum (SC), skin (dermis and epidermis), and receptor fluid (RF). The analytical method demonstrated excellent linearity (r² = 0.9915–0.9998), accuracy (87.3–113.6%), and precision (1.2–10.4%), meeting the validation criteria. Dermal absorption of picolinamide from a lotion formulation was evaluated using a Franz diffusion cell system. A 0.5% picolinamide lotion formulation was applied to mini-pig skin at a dose of 10 μL/cm². After 24 hours of exposure, the skin surface was wiped with swabs, and the stratum corneum was collected by tape stripping. The remaining skin was sectioned into eight pieces for analysis, and receptor fluid samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours. The total dermal absorption of picolinamide from the lotion formulation was determined to be 71.12 ± 29.35 μg/cm² (65.20 ± 25.74%). These findings provide essential data for estimating systemic exposure and supporting the safety assessment of picolinamide when used as a cosmetic ingredient.