Decompressive craniotomy (DC) is the most commonly performed procedure in cases of severe traumatic brain injury (TBI), space-occupying lesions (SOL) with malignant brain edema; especially in the pediatric age groups [1]. The time-tested therapy for rehabilitation of craniotomy defects is cranioplasty. Be that as it may, the timing of repair is still debated and remains controversial. The phenomenon of spontaneous regeneration of cranial defect although rare remains restricted to patients not later than 24 months of age. The occurrence of such an event becomes even rarer in patients elder than 24 months. To the best of the authors’ knowledge, this is the second reported case of spontaneous regeneration of a large craniotomy defect in a pediatric patient. A similar case has also been reported by Tran et al. [2] A six-year-old female child was presented by her parents to our institute for the reconstruction of cranial defect, 18 months post-DC for TBI. The post-DC computed tomogram (CT), which was obtained by the authors from the neurosurgical team, revealed a defect in the Fronto-temporoparietal region on the left measuring 118mm × 73mm × 58.9 (APXCCXTR) ( Fig. 1 ). Clinical evaluation of the patient revealed near-normal symmetry of the cranial vault and on palpation hard tissue in the DC site ( Fig. 2 ). Hard tissue was poorly delineated from DC bone margins, with well-circumcised areas of fibrous consistency. Subsequent CT with three-dimensional reconstruction revealed well-defined “islands” of spontaneous bone regeneration in the craniotomy area, which resembles a “river delta”. Owing to miraculous regeneration of bone, an unusual decision for deferment of cranioplasty was made. The child is planned for a 24- and 36-months follow-up. Presently, the patient was evaluated based on a functional Independence Measure (FIM) score of 55. Various methods for bone regeneration of such defects have been attempted including the use of Bone Morphogenetic protein-7 [3], Nevertheless, there are scant studies that can explain this rare phenomenon. A study by Greenwald et al. [4] suggests that the capacity for regeneration of bone later than 06 years is largely absent. The fact that underlying duramater or the overlying periosteal cambium layer that could have led to the regeneration of bone can only be theorized and need further evaluation. Cranial bones being intramembranous, the existence of multipotent stem cells in such bones, needs to be evaluated. The presence of these cells may account for the occurrence of such phenomenon which seems to have the potential to pave way for the rehabilitation of cranial defects by stimulation of such cells (see Fig. 3 ).