Egypt was recently exposed to a sever outbreak of Foot and Mouth Disease (FMD) in 2012 with a new introduced strain of the virus (SAT2). This study concerned with diagnosis of FMD by using some recent methods in addition to the traditional methods of diagnosis. A total of 326 animals were clinically examined in different localities at Sharkia Governorates; 301 animals showed clinical signs of FMD (diseased animals) and 25 animals were apparently healthy. The diseased animals consisted of 277 cattle and 24 buffaloes. Some of them were vaccinated with the FMD bivalent vaccine before the outbreak and others were not vaccinated. Eighty two  clinical samples (73 epithelial tissues (Epi.T.) and 9 vesicular fluids (V.F)) from cattle and buffaloes were isolated on Baby Hamster kidney (BHK-21) cell line and 76 samples (92.7%) were positive. By using FMDV ELISA Kits for typing the virus only serotype SAT2 was detected. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect SAT2 serotype in 10 sample collected from 5 diseased cattle and 5 diseased buffaloes from different localities. Only one sample showed negative reaction (this sample was also negative by virus isolation and ELISA typing). Serum samples were collected from the 301 animals at different times after the infection; the antibodies against FMDV non-structural protein were detected by FMDV′CHEK Test in 270 cases (89.7%) of examined animals, while antibodies against the structural protein were detected by SNT and ELISA where antibodies against serotypes O, A and SAT2 were detected in 75.7%, 75.7% and 100% of examined animals for each serotype respectively by both tests. Mixed infection with more than one serotype was only recorded at Al-Salhia dairy farm. It is concluded that combination between recent and traditional techniques for diagnosis of FMD help in accurate and rabid diagnosis and subsequently control the disease.