BACKGROUND Palmoplantar pustulosis (PPP) is initiated from the acrosyringium. However, it is unclear whether PPP should be considered a distinct entity or should be classified into the spectrum of pustular psoriasis, also known as palmoplantar pustular psoriasis (PPPP). OBJECTIVE We evaluated the differences in immunohistochemical staining in patients with PPP to determine whether they can be classified into two groups based on psoriatic properties or acrosyringeal properties. METHODS Nineteen punch biopsy specimens diagnosed with PPP were collected. Antibodies were chosen for identifying the acrosyringeal properties of α-3-nicotine acetylcholine receptors (α-3-nAChR), psoriatic properties of interleukin (IL)-23 and IL-36R, inflammatory cell properties of human cathelicidin antimicrobial peptide 18/LL-37, IL-8, lipocalin-2 (LCN2), and CD3. The degree of staining of the epidermis was evaluated using the ordinal scale (0~3). The principal component analysis was used to derive principal components (PCs) of common variation between the stains, and the two groups were divided using PCs and cluster analysis. RESULTS Three main PCs explained 64% of the total variance in PPP. PC1 (pustular psoriasis properties) showed a higher correlation with IL-36R. PC2 (acrosyringeal/inflammatory properties) showed a higher correlation with α-3-nAChR, IL-8, LCN2, and CD3. PC3 (psoriasis properties) showed a higher correlation with IL-23. PC1 showed a statistically significant difference (p=0.0284) between the two groups. We identified three PCs associated with the pathomechanisms of PPP. CONCLUSIONS Although PC1 showed a statistically significant difference between the two groups, we did not identify differential protein expression related to the pathogenesis between PPP and PPPP.