Background/Aim. Alarm features (AF) are of limited utility in predicting endoscopic findings, and the majority of pa-tients with uninvestigated dyspepsia will have no organic pa-thology identified at upper gastrointestinal endoscopy. In our previous study, we highlighted seroreactivity against Helicobac-ter pylori (HP) antigens VacA, 50 kDa, and 30 kDa as bi-omarkers for gastric cancer, peptic ulcers, and functional dys-pepsia. We designed and conducted this pilot study in order to compare the diagnostic utility of seroreactivity against HP VacA, 50 kDa, and 30 kDa with AF and investigate the pos-sibility and adequacy of its synchronous application. Method. A careful history and physical examination with special atten-tion to AF, esophagogastroduodenoscopy with biopsy, ab-dominal ultrasound or computer tomography, complete blood count (CBC) and blood biochemistry, a Western Blot IgG against HP antigens VacA, 50 kDa, and 30 kDa, were performed in 123 patients with dyspepsia: 31 with gastric can-cer, 31 with duodenal ulcer, 31 with gastric ulcer, and 30 with gastritis and functional dyspepsia. AF vs various combina-tions of seroreactivity against HP VacA, 50 kDa, and 30 kDa in patients with functional dyspepsia and others were ana-lyzed in this study. Synchronous and alternative seroreactivity against VacA, 50 kDa, and 30 kDa, along with/without AF in patients with functional dyspepsia and other groups of pa-tients were also analyzed. Results. VacA and 50 kDa sero-positivity or AF had excellent case-findings clinical utility in-dex for investigating dyspepsia. The absence of AF and sero-reactivity against VacA either with: 50 kDa or 30 kDa sero-positivity or 50 kDa and 30 kDa seropositivity had an excel-lent screening clinical utility index for investigating dyspepsia. Conclusion. Seroreactivity against HP antigens VacA, 50 kDa, and 30 kDa might improve our approach to patients in investigating dyspepsia if used along with AF.