The aim of this study was to assess the diagnostic accuracy of single photon emission tomography (SPECT) in unilateral condylar hyperplasia (UCH). To this end, 3D morphometric changes of the mandibles in one year were assessed (T0 vs. T1) and compared over SPECT results in T1, in a sample of 40 patients. A contingency table was constructed based on these results for SPECT diagnostic accuracy evaluation, classifying patients as SPECT true-positive, true-negatives, false positives and false-negatives. Additionally, the morphometric analysis was used to describe the presentation of mandibular changes using principal component analysis (PCA) and non-parametric statistics. We obtained diagnostic accuracy results of sensitivity 81%, specificity 63%, positive predictor value (PPV) 59%, negative predictor value (NPV) 83% and accuracy 70%, showing that SPECT yields poor results regarding accuracy diagnostic performance. The morphometric analysis showed that individuals without progress of asymmetry and those with more progress differ particularly in a group of landmarks representing the mental region and the right mandibular body. Based on these landmarks, difference among the four SPECT-accuracy groups was statistically significant (p < 0.001), where the landmark showing the largest change within a year had a mean increase of 1.13 + 0.66 mm. Within the limitations of the study, it seems that SPECT alone is not suitable for making surgical decisions regarding condylectomy in active UCH. Follow up with morphological assessment methods are recommended for confirming an active UCH in combination with SPECT.