Computed tomography (CT) is an important and widely used modality in the diagnosis and treatment of various cancers. In the field of molecular radiotherapy, the use of spongiosa volume (combined tissues of the bone marrow and bone trabeculae) has been suggested as a means to improve the patient-specificity of bone marrow dose estimates. The noninvasive estimation of an organ volume comes with some degree of error or variation from the true organ volume. The present study explores the ability to obtain estimates of spongiosa volume or its surrogate via manual image segmentation. The variation among different segmentation raters was explored and found not to be statistically significant (p value >0.05). Accuracy was assessed by having several raters manually segment a polyvinyl chloride (PVC) pipe with known volumes. Segmentation of the outer region of the PVC pipe resulted in mean percent errors as great as 15% while segmentation of the pipe's inner region resulted in mean percent errors within approximately 5%. Differences between volumes estimated with the high-resolution CT data set (typical of ex vivo skeletal scans) and the low-resolution CT data set (typical of in vivo skeletal scans) were also explored using both patient CT images and a PVC pipe phantom. While a statistically significant difference (p value <0.002) between the high-resolution and low-resolution data sets was observed with excised femoral heads obtained following total hip arthroplasty, the mean difference between high-resolution and low-resolution data sets was found to be only 1.24 and 2.18 cm3 for spongiosa and cortical bone, respectively. With respect to differences observed with the PVC pipe, the variation between the high-resolution and low-resolution mean percent errors was a high as approximately 20% for the outer region volume estimates and only as high as approximately 6% for the inner region volume estimates. The findings from this study suggest that manual segmentation is a reasonably accurate and reliable means for the in vivo estimation of spongiosa volume. This work also provides a foundation for future studies where spongiosa volumes are estimated by various raters in more comprehensive CT data