We present the unusual case of complex regional pain syndrome (CRPS) of the residual limb in a 54-year-old woman with transtibial lower-limb amputation. Intractable pain developed 14 months after amputation, followed by successful rehabilitation. Anamnesis and clinical findings included sensory symptoms, vasomotor symptoms and signs, and oedema. The Budapest criteria for a diagnosis of CRPS were met. After infusions of bisphosphonates during a 5-week inpatient interdisciplinary rehabilitation programme, the pain decreased. Clinicians should suspect CRPS in case of chronic or recurrent residual limb pain. The Budapest criteria seem applicable even if interpretation of symptoms and findings can be complicated in vascular polymorbid lower-limb amputation. Bisphosphonates, proposed as first-line pharmacological treatment, can be useful.