PURPOSE: In breast imaging, radiological in-vivo images, such as X-ray mammography and Magnetic Resonance Imaging (MRI), are used for tumour detection, diagnosis and size determination. After excision, the specimen is typically sliced into slabs and a small subset is sampled. Histopathological imaging of the stained samples is used as the gold standard for characterisation of the tumour microenvironment. A 3D volume reconstruction of the whole specimen from the 2D slabs could facilitate bridging the gap between histology and in-vivo radiological imaging. This task is challenging however, due to the large deformation that the breast tissue undergoes after surgery and the significant undersampling of the specimen obtained in histology. In this work we present a method to reconstruct a coherent 3D volume from 2D digital radiographs of the specimen slabs. METHODS: To reconstruct a 3D breast specimen volume, we propose the use of multiple target neighbouring slices, when deforming each 2D slab radiograph in the volume, rather than performing pairwise registrations. The algorithm combines neighbourhood slice information with Free Form Deformations, which enables a exible, non-linear deformation to be computed subject to the constraint that a coherent 3D volume is obtained. The neighbourhood information provides adequate constraints, without the need for any additional regularisation terms. RESULTS: The volume reconstruction algorithm is validated on clinical mastectomy samples using a quantitative assessment of the volume reconstruction smoothness and a comparison with a whole specimen 3D image acquired for validation before slicing. Additionally, a target registration error of 5 mm (comparable to the specimen slab thickness of 4 mm) was obtained for five cases. The error was computed using manual annotations from four observers as gold standard, with inter-observer variability of 3.4 mm. Finally, we illustrate how the reconstructed volumes can be used to map histology images to a 3D specimen image of the whole sample (either MRI or CT). CONCLUSIONS: Qualitative and quantitative assessment has illustrated the benefit of using our proposed methodology to reconstruct a coherent specimen volume from serial slab radiographs. To our knowledge this is the first method that has been applied to clinical breast cases, with the goal of reconstructing a whole specimen sample. The algorithm can be used as part of the pipeline of mapping histology images to ex-vivo and ultimately in-vivo radiological images of the breast.