The study assessed the applicability of utilizing a newly introduced non-anatomical soft and hard tissue centroid line (S&H centroid) in differentiating between sagittal and vertical cephalometric skeletal intermaxillary relationship in a heterogeneous sample. The sample consisted of 87 lateral cephalometric radiographs size 12" x 14" of subjects with a mixed sagittally; skeletal Class I, II and III and vertically; skeletal horizontal and steep mandibular planes. The mean values of the sagittal and vertical maxillary and mandibular measurements were established and statistically investigated. Pearson correlation co-efficient was used to assess the reliability. One Way ANOVA and Tukey Multiple Comparison Post Hoc test with significant level at P<0.05 were also used. The findings were also statistically compared to a previously reported findings of a homogenous sample, using independent t-test at P<0.05. The results indicated high intra examiner reliability, with correlation co-efficient between 0.00 – 1.00. The centroid based reference line has the ability to evaluate and statistically differentiate between the sagittal and vertical intermaxillary relationships in both heterogeneous and homogenous samples. In conclusions the findings tend to confirm the applicability or usefulness of the (S&H centroid) line in the cephalometric skeletal evaluation. 1 Associate Professor, Division of Orthodontics, Department of Pediatric Dentistry and Orthodontics, King Saudi University, College of Dentistry, Riyadh 2 Intern, King Saudi University, College of Dentistry, Riyadh Correspondence: Dr Khalid Al-Balkhi, PO Box 60169, Riyadh 11545, Kingdom of Saudi Arabia. Email: kalbalkhi@KSU.EDU.SA.