A case of necrotizing ulcerative periodontitis (NUP), the most severe inflammatory periodontal disorder caused by plaque bacteria, is shown. Clinically, the gingiva showed distinct signs of ulceration, and radiography revealed horizontal bone loss. Indirect immunofluorescence, carried out on frozen sections of tissue specimens obtained from the NUP lesion, exhibited clear expression of atypical keratin K19, particularly in basal cells, when compared to noninflamed gingiva. Moreover, NUP tissue showed extensive intraepithelial abundance for the basement membrane component laminin-1/10 and the extracellular matrix molecule tenascin. Strong expression of integrin subunit αv and matrix metalloproteinase-13 in conjunction with interleukin 1-beta further discriminated NUP gingival epithelium from normal tissue. The results suggest that NUP is associated with changes in the expression and topography of the analyzed molecules in the gingival epithelium, which in turn may reflect the fast progression of the disease.