Researchers at the CDC and Lawrence Livermore National Laboratory published results this month indicating that smallpox is older than previous estimations.
Collaborators at the labs sequenced genomes of 47 geographic isolates of smallpox gathered between 1946 and 1977. Comparison of the rates of random mutations (single nucleotide polymorphisms, or SNPs) allowed the scientists to calibrate a "molecular clock" which suggests the strain diverged either 16,000 or 68,000 years ago. The large disparity in the estimated dates depends on whether data from East Asia or Africa is used to calibrate the molecular clock.
Check out the news release describing the results here.
I'm not very sure how accurate these molecular clocks are... it's interesting to think that smallpox spread westward from East Asia, since some of the oldest descriptions of smallpox-like disease come from ancient China.