Pyostomatitis-pyodermatitis vegetans is a mucocutaneous disease characterized by the occurrence of multiple pustules and considered a strong clinical marker for inflammatory bowel disease, which represents chronic inflammatory disorders of the digestive tract, more often comprising Crohn’s disease and ulcerative colitis. In the oral cavity, pyostomatitis vegetans more commonly manifests in the buccal and labial mucosa, followed by gingival tissues as edematous mucosa with multiple miliary sterile pustules that may rupture and result in confluent, painful, superficial yellowish pustules and erosions leading to the so-called “snail track” lesions. Male patients are slightly more affected than females, more often during the fourth to sixth decades of life. Simultaneous eosinophilia and cutaneous lesions are reported to be present in more than 50% of the cases affecting the oral mucosa. Microscopically, there is an epithelial cleft with acantholytic cells and a dense infiltrate of neutrophils and eosinophils. Although pyostomatitis vegetans can be effectively controlled by intestinal bowel disease treatment, there is currently no standard protocol established for managing these patients. Different therapeutic protocols are reported in the literature, ranging from topical and/or systemic steroids, monoclonal antibodies, immunosuppressive agents, antibiotics, or a combination of these different approaches.