BACKGROUND: Seborrheic dermatitis (SD) is a common, chronic inflammatory skin disease with limited understanding of its pathophysiology. Molecular profiling has been limited by invasiveness of sampling methods. OBJECTIVE: To analyze the molecular skin profile of adult patients with SD using tape strips. METHODS: Tape-strips obtained from facial lesions of 26 adult SD patients and 18 demographically matched healthy controls were evaluated with RNA sequencing. RESULTS: SD molecular skin fingerprint was characterized by strong and significant upregulation of interleukin (IL)23/T-helper (Th)17 and Th22 (i.e. IL23A, IL22, PI3, LL37, S100A8, S100A12), some Th1 skewing (OASL, STAT1, CXCL9), and limited Th2 modulation. A parallel downregulation of barrier markers (CLDN1/8, FA2H, ELOVL3) was also observed. LIMITATIONS: Limited representation of mild and severe SD patients. CONCLUSION: These data deepen our understanding of SD suggesting that it has robust Th17/Th22, some Th1 skewing, and minimal Th2 activation, and associated skin barrier alterations. This provides rationale for novel immunomodulatory treatment approaches for SD patients targeting IL23/Th17 and/or Th22 pathways.