Amyloidosis is the most grievous manifestation of Familial Mediterranean Fever (FMF), occurring in a high proportion of untreated patients. Continuously elevated serum amyloid A (SAA) levels during remissions, rather than a pulsatile rise during FMF attacks, underlies the development of amyloidosis. FMF phenotype II is one extreme of AA amyloidosis, evolving despite a complete absence of FMF attacks. FMF phenotype II is diagnosed in patients with AA amyloidosis in the context of a family history of FMF. In these patients and in patients with AA amyloidosis without family history of FMF and with unknown precipitating disease, MEFV gene analysis is mandatory. Moreover, since FMF phenotype II is an actual hazard, a cost-benefit analysis suggests that MEFV mutation determination in all first-degree family members of FMF patients is warranted, as it will significantly reduce future patient treatment costs.