Fanconi anemia (FA) is a rare inherited recessive disease caused by mutations in 
one of fifteen genes known to encode FA pathway components. In response to DNA 
damage, nuclear FA proteins associate into high molecular weight complexes 
through a cascade of post-translational modifications and physical interactions, 
followed by the repair of damaged DNA. Hematopoietic cells are particularly 
sensitive to the loss of these interactions, and bone marrow failure occurs 
almost universally in FA patients. FA as a disease is further characterized by 
cancer susceptibility, which highlights the importance of the FA pathway in 
tumor suppression, and will be the focus of this review. Acute myeloid leukemia 
is the most common cancer type, often subsequent to bone marrow failure. 
However, FA patients are also at an extreme risk of squamous cell carcinoma 
(SCC) of the head and neck and gynecological tract, with an even greater 
incidence in those individuals who have received a bone marrow transplant and 
recovered from hematopoietic disease. FA tumor suppression in hematopoietic 
versus epithelial compartments could be mechanistically similar or distinct. 
Definition of compartment specific FA activities is now critical to assess the 
effects of today's bone marrow failure treatments on tomorrow's solid tumor 
development. It is our hope that current therapies can then be optimized to 
decrease the risk of malignant transformation in both hematopoietic and 
epithelial cells. Here we review our current understanding of the mechanisms of 
action of the Fanconi anemia pathway as it contributes to stress responses, DNA 
repair and squamous cell carcinoma susceptibility.