Familial Mediterranean is a genetic health problem inherited through recessive autosomal transmission. It may cause serious long-term morbidity and mortality. The goal of this research is to survey the most widespread MEFV gene mutations in a large population of Egyptian patients suspected of having FMF disease. 2056 patients were tested for the 13 most prevalent types of MEFV mutations found in the basin of the Mediterranean using real-time PCR. Results: Our results showed that fever was reported as the most prevalent clinical feature (94.5%), followed by abdominal pain (90.0%) and arthritis (59.4%). Only 1017 patients (49.5%) had positive MEFV gene mutations (754 males and 263 females), while 1039 patients (50.5%) showed negative mutations for the 13 most prevalent types of MEFV gene mutations in Egypt. Conclusion: We suggested that F479L mutation analysis shouldn’t be added to the routine molecular diagnosis of FMF patients. Depending on screening of the most prevalent mutations of MEFV gene in Egypt is not a sufficient confirmatory test for diagnosis of FMF in suspected patients and sequencing the entire MEFV gene is recommended. Most positive patients for the MEFV prevalent mutations were heterozygous.