Serum anti-Helicobacter pylori antibodies and pepsinogens (PGs) have been used as gastric cancer screening and gastric mucosal status markers. Nepal is a low risk country for gastric cancer. However, the mountainous populace in the northern region culturally linked to Tibet as well as Bhutan, a neighboring country, have a high risk of GC. We collected gastric biopsy specimens and sera from 146 dyspeptic patients living in Kathmandu, Nepal. We also examined the sera of 80 volunteers living in the mountainous regions of the Himalayas. The optimal cut-off was calculated for serum biomarkers against the histology. Kathmandu patients (43.8%) were serologically positive for H. pylori infection, which was significantly lower than that for the mountainous (61.3%, P = 0.01). The same results also found in the prevalence of PG-positivity, PG I levels and PG I/II ratios (P = 0.001, P <0.0001 and P = 0.03, respectively). Moreover, the PG I/II ratios were significantly, and inversely correlated with the OLGA score (r = -0.33, P <0.009). The low incidence of gastric cancer in Nepal can be attributed to low gastric mucosal atrophy. However, the mountainous subjects have high-risk gastric mucosal status, which could be considered a high-risk population in Nepal.