Histidine-rich protein 2 (HRP2) detecting rapid diagnostic tests (RDTs) have played an important role in enabling prompt malaria diagnosis in remote locations. HRP2 has advantages over other biomarkers because of its abundance in the bloodstream, repetitive binding epitopes, and falciparum-specificity. Most HRP2-based RDTs also exhibit some cross-reactivity to a closely related protein (HRP3). Plasmodium falciparum parasites lacking HRP2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs. The objective of the study was to study the sensitivity and specificity of hrp2-based RDT for diagnosis of falciparum, to compare the RDT results with microscopy and polymerase chain reaction (PCR), and to determine the prevalence of HRP2 gene deletion among the RDT-negative, microscopy-positive falciparum strains. Blood samples were collected and diagnosis was done by microscopic examination, RDTs, and PCR. Out of 1000 patients examined, 138 were positive for P. falciparum. Fever was the most common symptom followed by chills with rigor and headache were recorded among more than >95% of the study patients. Three microscopy-confirmed P. falciparum cases were negative by HRP2-based RDT and were found to have deletion of HRP2 and HRP3 exon 2. Rapid and accurate diagnosis and prompt deployment of effective antimalarial medication are essential components of appropriate case management. P. falciparum strains that evade diagnosis by RDTs represent a major threat to malaria control and elimination efforts.