Multileaf collimator (MLC)-assisted intensity modulated radiotherapy (IMRT) has greatly improved the target coverage and avoidance of organs at risk (OAR) for the treatment of nasopharyngeal carcinoma; however, its implementation is also constrained by the features of the MLC. Nasopharyngeal carcinoma tends to have a large gross target volume (GTV) and clinical target volume (CTV) due to its biological characteristics. More than one isocenter may be needed when small MLCs (i.e., BrainLAB M3, whose largest field is 10 x 10 cm(2)) are used to treat the nasopharyngeal carcinoma. The BrainLAB IMRT system was used to evaluate the effectiveness of a multi-isocenter IMRT plan for treating nasopharyngeal cancers. Dose coverage of GTVs and CTVs were compared among IMRT plans with 1, 2 and 3 isocenters, as were dose objectives for OARs including brainstem, cord, and parotids. The dosimetric variation and the delivery time were also measured with a phantom. IMRT plans with more than 1 isocenter achieved a better dose coverage, homogeneity, and conformity on GTVs and CTVs; however, with risk of higher doses given to OARs. In most cases, one can generate satisfactory IMRT plans using the 2-isocenter IMRT planning strategy. Two-isocenter planning strategy may be a suitable compromise when more isocenters are needed.