Helicobacter pylori (H. pylori)is a gram-negative aerobic pathogen that primarily colonizes the gastric mucosa. Peptic ulcer disease, atrophic gastritis, gastric cancer, and mucosal-associated lymphoid tissue lymphoma have all been linked to chronicH. pyloriinfection. Hence, it is critical to diagnose and treat it as early as possible. There are both invasive and noninvasive tests available to detect it. In this review, the diagnostic abilities of two invasive tests - histology and the rapid urease test (RUT) - are compared in a variety of clinical situations.This systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 checklist. We performed a literature search using the PubMed and Google Scholar databases in accordance with the eligibility criteria and ultimately selected eight articles for final analysis. The Newcastle-Ottawa scale adapted for cross-sectional studies, the Scale for the Assessment of Narrative Review Articles (SANRA), and the PRISMA 2020 checklist were used to assess the quality of selected articles for cross-sectional studies, traditional literature reviews, and systematic reviews, respectively. According to the findings of the review, both histology and the RUT have high sensitivity and specificity in diagnosingH. pylorithough this varies depending on the clinical situation, making one test superior to the other. Neither of these tests can be considered the gold standard method on its own. Hence, using at least two diagnostic tests at the same time is critical for ensuring high sensitivity and specificity while accurately diagnosing the pathogen.