Introduction: Magnetic Resonance Spectroscopy (MRS)is a potentially useful adjunct to Magnetic Resonance Imaging (MRI) in thecharacterization of focal brain lesions. This study was aimed at showing that by the additional use of MRS (MRI, MRS), the characterization of a focal brain lesion into neoplastic, or non- neoplastic (infective, or degenerative) can be improved, as compared to the use of MRI alone. Study question: Does the additional use of MRS improve MRI differentiation of neoplastic from non- neoplastic (infective or degenerative) focal brain lesions? Methods: The design was prospective, analytical and comparative. 80 consecutive patients were enrolled. Conventional MRI of the brain was performed then a single voxel proton MRS spectrum was applied to a focal brain lesion. A similar MRS spectrum was subsequently acquired from the contra-lateral normal area of the brain, for comparison. The MRI examination, followed by the MRI, MRS examination was then interpreted by two consultant radiologists and a resident radiologist in consensus. Kappa measurement of agreement was used to determine the agreement between the MRI and MRI, MRS with the final diagnosis. Sensitivity, specificity, positive predictive values and accuracy of the two tests were calculated. The difference between the number of indeterminate lesions in the two tests was noted. Logistic regression demonstrated the role of confounding factors in the diagnostic use of MRS. Results: Of the eighty patients initially recruited, seventy four (92.5%) were analyzed, and six were lost to follow- up. According to the final diagnosis, 33% of the lesions were infections, 29% neoplastic, 37% degenerative and, 1% were indeterminate. On the basis of the kappa analysis, MRI, MRS had an increase in agreement of 7.4% compared to MRI and the confidence levels of the two tests did not overlap. The sensitivity of MRI, MRS was 4.82 times greater than that of MRI. MRI, MRS had a 1.7% increase in accuracy. The combined test reduced the indeterminate MRI lesions by 5.4%. Logistic regression showed that for lesions which were enhancing, MRS yield was more helpful if the voxel position included the enhancing part. Conclusion: The additional use of single voxel MRS improves the MRI characterization of neoplastic from non- neoplastic (infectious or degenerative) focal brain lesions. It is most useful as an additional protocol to conventional MRI in the characterization of neoplastic from non- neoplastic brain lesions.