Background: Facial pain in multiple sclerosis is often due to trigeminal neuralgia but atypical pictures can be observed. Case presentation: A man with primary progressive multiple sclerosis developed severe unilateral facial pain in the right orbital region. Spontaneous and triggered attacks were associated with ipsilateral conjunctival injection and lacrimation. A diagnosis of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing was made, and symptoms significantly improved with lamotrigine. Conclusion: Pain is poorly investigated in multiple sclerosis, with a dramatic impact on patients’ life quality. In this light, standardized evaluation of pain is needed to improve patient management.