Background Early-stage pemphigus vulgaris (PV) often manifests as erythema alone. We hypothesized that very high-frequency ultrasonography (VHFUS) features could simplify the differential diagnosis of early-stage pemphigus vulgaris versus seborrheic dermatitis (SD). Materials and Methods Fourteen patients with SD or early-stage PV were recruited from our outpatient clinic during 2016-2019. We used 50-MHz VHFUS to image the erythema on the patients' scalp, face, chest, and back and retrospectively evaluated their ultrasonographic features. Results Very high-frequency ultrasonography images of early-stage PV showed enhanced epidermal echo (8/14, 57%), linear or oval intra-epidermal hypoechoic/anechoic areas (12/14, 86%), linear anechoic areas at the dermal-epidermal junction (14/14, 100%), reduced echo of superficial to whole dermis (9/14, 64%), and slightly increased dermal thickness (14/14, 100%). The intra-epidermal hypoechoic/anechoic bands (100%) showed the greatest specificity. VHFUS images of SD showed enhanced epidermal echo (7/14, 50%), epidermal unevenness (7/14, 50%), linear anechoic bands at the dermal-epidermal junction (8/14, 57%), reduced middle dermis echo (10/14, 71%), and slightly increased dermal thickness (10/14, 71%). The epidermal unevenness (100%) had the greatest specificity. There was a significant difference (P < .05) between early-stage PV and SD regarding the proportion of linear intraepithelial hypoechoic/anechoic bands and linear anechoic areas at the dermal-epidermal junction. Conclusions Early-stage PV and SD have relatively specific VHFUS erythematous manifestations. Intra-epidermal hypoechoic/anechoic bands for early-stage PV and epidermal unevenness for SD were most specific. VHFUS contributes to the differential diagnosis of PV and SD by highlighting their features, that is, intra-epidermal hypoechoic/anechoic bands and linear anechoic areas at the dermal-epidermal junction.