Motivation: Tiled serial section Transmission Electron Microscopy (ssTEM) is increasingly used to describe high-resolution anatomy of large biological specimens. In particular in neurobiology, TEM is indispensable for analysis of synaptic connectivity in the brain. Registration of ssTEM image mosaics has to recover the 3D continuity and geometrical properties of the specimen in presence of various distortions that are applied to the tissue during sectioning, staining and imaging. These include staining artifacts, mechanical deformation, missing sections and the fact that structures may appear dissimilar in consecutive sections. Results: We developed a fully automatic, non-rigid but as-rigid-as-possible registration method for large tiled serial section microscopy stacks. We use the Scale Invariant Feature Transform (SIFT) to identify corresponding landmarks within and across sections and globally optimize the pose of all tiles in terms of least square displacement of these landmark correspondences. We evaluate the precision of the approach using an artificially generated dataset designed to mimic the properties of TEM data. We demonstrate the performance of our method by registering an ssTEM dataset of the first instar larval brain of Drosophila melanogaster consisting of 6885 images.